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1.
PRMT1 Sustains De Novo Fatty Acid Synthesis by Methylating PHGDH to Drive Chemoresistance in Triple-Negative Breast Cancer.
Yamamoto, T, Hayashida, T, Masugi, Y, Oshikawa, K, Hayakawa, N, Itoh, M, Nishime, C, Suzuki, M, Nagayama, A, Kawai, Y, et al
Cancer research. 2024;(7):1065-1083
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Abstract
UNLABELLED Triple-negative breast cancer (TNBC) chemoresistance hampers the ability to effectively treat patients. Identification of mechanisms driving chemoresistance can lead to strategies to improve treatment. Here, we revealed that protein arginine methyltransferase-1 (PRMT1) simultaneously methylates D-3-phosphoglycerate dehydrogenase (PHGDH), a critical enzyme in serine synthesis, and the glycolytic enzymes PFKFB3 and PKM2 in TNBC cells. 13C metabolic flux analyses showed that PRMT1-dependent methylation of these three enzymes diverts glucose toward intermediates in the serine-synthesizing and serine/glycine cleavage pathways, thereby accelerating the production of methyl donors in TNBC cells. Mechanistically, PRMT1-dependent methylation of PHGDH at R54 or R20 activated its enzymatic activity by stabilizing 3-phosphoglycerate binding and suppressing polyubiquitination. PRMT1-mediated PHGDH methylation drove chemoresistance independently of glutathione synthesis. Rather, activation of the serine synthesis pathway supplied α-ketoglutarate and citrate to increase palmitate levels through activation of fatty acid synthase (FASN). Increased palmitate induced protein S-palmitoylation of PHGDH and FASN to further enhance fatty acid synthesis in a PRMT1-dependent manner. Loss of PRMT1 or pharmacologic inhibition of FASN or protein S-palmitoyltransferase reversed chemoresistance in TNBC. Furthermore, IHC coupled with imaging MS in clinical TNBC specimens substantiated that PRMT1-mediated methylation of PHGDH, PFKFB3, and PKM2 correlates with chemoresistance and that metabolites required for methylation and fatty acid synthesis are enriched in TNBC. Together, these results suggest that enhanced de novo fatty acid synthesis mediated by coordinated protein arginine methylation and protein S-palmitoylation is a therapeutic target for overcoming chemoresistance in TNBC. SIGNIFICANCE PRMT1 promotes chemoresistance in TNBC by methylating metabolic enzymes PFKFB3, PKM2, and PHGDH to augment de novo fatty acid synthesis, indicating that targeting this axis is a potential treatment strategy.
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Validation of Dietary Intake Estimated by Web-Based Dietary Assessment Methods and Usability Using Dietary Records or 24-h Dietary Recalls: A Scoping Review.
Murai, U, Tajima, R, Matsumoto, M, Sato, Y, Horie, S, Fujiwara, A, Koshida, E, Okada, E, Sumikura, T, Yokoyama, T, et al
Nutrients. 2023;(8)
Abstract
The goal was to summarize studies comparing the accuracy of web-based dietary assessments with those of conventional face-to-face or paper-based assessments using 24-h dietary recall or dietary record methods in the general population. Using two databases, mean differences and correlation coefficients (CCs) for intakes of energy, macronutrients, sodium, vegetables, and fruits were extracted from each study independently by the authors. We also collected information regarding usability from articles reporting this. From 17 articles included in this review, the mean dietary intake differences in the web-based dietary assessment compared to conventional methods, were -11.5-16.1% for energy, -12.1-14.9% for protein, -16.7-17.6% for fat, -10.8-8.0% for carbohydrates, -11.2-9.6% for sodium, -27.4-3.9% for vegetables, and -5.1-47.6% for fruits. The CC was 0.17-0.88 for energy, protein, fat, carbohydrates, and sodium, and 0.23-0.85 for vegetables and fruits. In three out of four studies reporting usability, more than half of the participants preferred the web-based dietary assessment. In conclusion, % difference and CC of dietary intake were acceptable in both web-based dietary records and 24-h dietary recalls. The findings from this review highlight the possibility of wide-spread application of the web-based dietary assessment in the future.
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National Nutrition Surveys Applying Dietary Records or 24-h Dietary Recalls with Questionnaires: A Scoping Review.
Okada, E, Nakade, M, Hanzawa, F, Murakami, K, Matsumoto, M, Sasaki, S, Takimoto, H
Nutrients. 2023;(22)
Abstract
Development of an accurate and efficient dietary method is required for national nutrition surveys. Some countries conduct dietary surveys and combine 24-h dietary records or 24-h dietary recalls with dietary questionnaires. This scoping review aimed to summarize studies that used results from national surveys that combined detailed dietary surveys (dietary records or 24-h dietary recall) and dietary questionnaires and identify the purpose of combining the two methods. The PubMed database and manual searches were used for the literature review. We extracted 58 articles from 16 national nutrition surveys from 14 countries. Most studies used 24-h dietary recall for detailed dietary surveys and the food frequency questionnaire (FFQ) or food propensity questionnaire (FPQ) for questionnaire surveys. Among 37 studies from eight countries, the purpose of combining the two dietary survey methods was to estimate energy and nutrient intakes from detailed dietary surveys and habitual food intake from questionnaires. These findings are useful as a reference when introducing new dietary survey methods in future national nutrition surveys.
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Delayed Eating Schedule Raises Mean Glucose Levels in Young Adult Males: a Randomized Controlled Cross-Over Trial.
Hatamoto, Y, Tanoue, Y, Yoshimura, E, Matsumoto, M, Hayashi, T, Ogata, H, Tanaka, S, Tanaka, H, Higaki, Y
The Journal of nutrition. 2023;(4):1029-1037
Abstract
BACKGROUND Misalignment of meals to the biological clock may cause adverse effects on glucose metabolism. However, the effects of repeated different eating schedules (early compared with late) on glucose concentration throughout the day are poorly understood. OBJECTIVES We examined the effects of different eating schedules on the 24-h glucose response using a continuous glucose monitor (CGM). METHODS Eight young adult males (age, 20.9 ± 3.4 y; body mass index: 21.3 ± 1.8 kg/m2) each followed 2 different eating schedules (early [08:30, 13:30, and 19:30] and late [12:00, 17:00, and 23:00]) in random order. These diet interventions were conducted for 8 d, with an experimental period of 3 d and 2 nights (from dinner on day 7) after 7 d of free living. The 3 meals in each intervention were nutritionally equivalent (55% carbohydrate, 15% protein, and 30% fat). The 24-h mean interstitial glucose concentration on day 8 was obtained under controlled conditions using the CGM (primary outcome). These concentrations were compared among the following 3 schedules using Dunnett's test, with the early eating schedule as reference (1 compared with 2 and 1 compared with 3): 1) early eating schedule (control), 2) late eating schedule according to the clock time (08:00 on day 8 to 08:00 on day 9), and 3) late eating schedule according to the time elapsed since the first meal for 24 h. RESULTS The 24-h mean ± SD interstitial glucose concentrations when participants followed the late eating schedule were higher than those when they followed the early eating schedule in terms of clock time (91.2 ± 2.9 compared with 99.2 ± 4.6 mg/dL, P = 0.003) and time elapsed (91.2 ± 2.9 compared with 98.3 ± 3.8 mg/dL, P < 0.001). CONCLUSIONS A late eating schedule increases the mean 24-h interstitial glucose concentration in young adult males. This insight will have useful implications in determining meal timings, especially for those with conditions such as diabetes.
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[How accurate are self-reported anthropometrics among the Japanese? A scoping review].
Aoyama, T, Yuan, X, Matsumoto, M, Okada, E, Okada, C, Takimoto, H
[Nihon koshu eisei zasshi] Japanese journal of public health. 2023;(12):817-827
Abstract
Objectives Monitoring of obesity and underweight prevalence in general populations is crucial for the implementation of effective public health measures. Self-reported height and weight values are often used to assess the body mass index (BMI) in such epidemiological surveillance. However, it is known that using self-reported height and weight may underestimate the prevalence of obesity (BMI≥25 kg/m2), while its accuracy for underweight (BMI<18.5 kg/m2) prevalence is not well-understood. The aim of this study was to conduct a scoping review on the accuracy of self-reported anthropometrics in the Japanese population, where both obesity and underweight are prevalent.Methods Using PubMed and CiNii Research, a literature search was conducted for studies published in English or Japanese by 2022 that were conducted in Japan and compared self-reported and measured height, weight, or/and BMI. The study design and mean reported errors (mean of reported values-mean of measured values) were extracted and tabulated, and differences by BMI categories were also considered.Results A total of 17 studies, with 11 being published in English, were included in this review. These studies were conducted in nationwide cohort studies (n=4), local populations (n=4), workplaces (n=3), and educational institutions (n=6), with diverse age ranges (10-91 years) and sample sizes (<100 to >30,000). Although the degree of mean reporting error varied between studies, most of the studies reported that height was overreported, weight was underreported, and BMI was underestimated. In the three studies that reported mean reporting errors by BMI category, the direction of reporting error for height remained consistent across all body size categories, while weight and BMI were overreported and overestimated only among the underweight. Four studies in adults showed that 14.2-37.6% of actually obese individuals and 11.1-32.3% of underweight individuals were misclassified as 'normal range' (18.5≤BMI<25 kg/m2) based on self-reporting, while 0.8-5.4% and 1.2-4.1% of individuals actually within the normal range were misclassified as 'underweight' and 'obese' based on self-report, respectively.Conclusion This study suggests that using BMI based on self-reported height and weight can underestimate the prevalence of both obesity and underweight in the Japanese population. These biases should be taken into consideration when using self-reported anthropometrics in epidemiological studies.
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Global Comparison of Nutrient Reference Values, Current Intakes, and Intake Assessment Methods for Sodium among the Adult Population.
Koshida, E, Tajima, R, Matsumoto, M, Takimoto, H
Journal of nutritional science and vitaminology. 2023;(1):38-45
Abstract
Excess sodium intake is a risk factor for non-communicable diseases (NCDs), such as cardiovascular diseases and hypertension. Therefore, many countries have set nutrient reference values for sodium, specifically for the prevention of NCDs, and intake is routinely monitored by nutrition surveys. In this review, we aimed to compare the global nutrient reference values and national intakes of sodium, along with the methods of intake assessment used. Data were obtained for Australia, Canada, Ireland, Japan, the UK, the US, and the European Food Safety Authority (EFSA), where information was accessible online in English or Japanese. We collected the following information regarding sodium intake: the term used for reference values to prevent NCDs; year when reference values were established or revised; reference values to prevent NCDs; target NCDs; designation of nutrition survey; method for estimating intake; and average intake. The reference values ranged from 2,000 mg (Australia and EFSA) to 2,953 mg (Japan). Sodium intake ranged from 2,431 mg (Australia) to 3,958 mg (Japan). Out of seven countries/institutions, five used dietary assessment, and two used sodium urinary excretion for estimating dietary sodium intake. Among the dietary assessment methods, the 24-h dietary recall was most frequently used. National sodium intake exceeded the reference values in all countries, and reduction of sodium intake remains a global challenge.
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Evaluation of protein requirements using the indicator amino acid oxidation method: a scoping review.
Matsumoto, M, Narumi-Hyakutake, A, Kakutani, Y, Tsuji, M, Hatamoto, Y, Higaki, Y, Sasaki, S
The Journal of nutrition. 2023;(12):3472-3489
Abstract
BACKGROUND The indicator amino acid oxidation (IAAO) method has been accepted as an approach to evaluate habitual protein requirements under free-living conditions. OBJECTIVES This scoping review reports on literature that evaluated protein requirements in humans using the IAAO methods. METHODS Three databases (PubMed/Medline, Web of Science, and ProQuest) were systematically searched to identify studies that evaluated protein requirements using the IAAO method published in English until 5 June, 2023. We evaluated the study quality using previously developed criteria. We extracted the characteristics of the study design and the results of protein requirements. Two reviewers conducted both reviews and quality assessments independently; any differences among them were resolved by consensus or agreement of all team members. RESULTS We extracted 16 articles targeting children, young adults (including pregnant women, resistance training athletes, endurance-training athletes, and team sports), and older adults. In quality assessment, 14 studies were evaluated "strong," but the remaining 2 were "moderate." These studies were conducted in only 3 countries and did not include all sexes or life stages. The range of the estimated average protein requirements of each life stage was 1.30 g/kg body weight/d for children, 0.87 to 2.10 (0.87-0.93 for general young adults, 1.22-1.52 for pregnant women, 1.49-2.00 for resistance-trained athletes, 1.65-2.10 for endurance athletes, and 1.20-1.41 for team sports athletes) g/kg body weight/d for young adults, and 0.85 to 0.96 g/kg body weight/d for older adults. CONCLUSIONS Protein requirements in 14 studies were higher than the current reference for each sex, life stage, and physical activity that are related to protein requirements. In the future, protein requirements of various populations including sex and life stage could be assessed using the IAAO methods worldwide.
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Prevalence and clinical outcomes of vitamin D deficiency among Japanese multiple myeloma patients: a single-center observational study.
Isoda, A, Miyazawa, Y, Ishikawa, T, Kanaya, S, Nakayama, K, Mihara, M, Iriuchishima, H, Saito, A, Matsumoto, M, Sawamura, M
Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer. 2023;(9):547
Abstract
PURPOSE Vitamin D plays a crucial role in skeletal metabolism and holds significant importance in the pathophysiology of multiple myeloma (MM). This study aimed to determine the prevalence of vitamin D deficiency among Japanese MM patients and its correlation with clinical outcomes. METHODS Serum 25-hydroxyvitamin D (25(OH)D) levels were assessed in 68 MM patients at a single institution in Japan, analyzing their association with clinical status, laboratory parameters including procollagen type 1 N-propeptide (P1NP) and tartrate-resistant acid phosphatase 5b (TRACP-5b), health-related quality of life (HR-QOL) scores, and overall survival. Additionally, patients with suboptimal 25(OH)D levels received cholecalciferol supplementation (1000 IU/day), and changes in laboratory parameters were monitored. RESULTS The median 25(OH)D level was 22 ng/ml, with 32% and 51% of patients exhibiting vitamin D deficiency (< 20 ng/ml) and insufficiency (20-29 ng/ml), respectively. The 25(OH)D levels were unrelated to sex, age, MM stage, or bone lesions, but the vitamin D-deficient group showed a tendency towards lower HR-QOL scores. Among patients achieving complete remission, vitamin D supplementation increased P1NP, while TRACP-5b remained unchanged. Overall survivals from vitamin D measurement and from MM diagnosis were significantly worse in the vitamin D-deficient group compared to the vitamin D-insufficient/-sufficient group. CONCLUSION The study identified a considerable number of Japanese MM patients with insufficient serum vitamin D levels, with one-third being deficient. Additionally, vitamin D deficiency predicted poor overall survival in Japanese MM patients. Further investigation is required to determine whether vitamin D supplementation can improve the frailty and survival of vitamin D-deficient MM patients.
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Effects of Intestinal Bacterial Hydrogen Gas Production on Muscle Recovery following Intense Exercise in Adult Men: A Pilot Study.
Eda, N, Tsuno, S, Nakamura, N, Sone, R, Akama, T, Matsumoto, M
Nutrients. 2022;(22)
Abstract
This study aimed to examine the effects of hydrogen gas (H2) produced by intestinal microbiota on participant conditioning to prevent intense exercise-induced damage. In this double-blind, randomized, crossover study, participants ingested H2-producing milk that induced intestinal bacterial H2 production or a placebo on the trial day, 4 h before performing an intense exercise at 75% maximal oxygen uptake for 60 min. Blood marker levels and respiratory variables were measured before, during, and after exercise. Visual analog scale scores of general and lower limb muscle soreness evaluated were 3.8- and 2.3-fold higher, respectively, on the morning after treatment than that before treatment during the placebo trial, but not during the test beverage consumption. Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) concentrations and production rates significantly increased with placebo consumption; no changes were observed with test beverage consumption. After exercise, relative blood lactate levels with H2-producing milk consumption were lower than those with placebo consumption. A negative correlation was observed between the variation of 8-OHdG and the area under the curve (AUC) of breath H2 concentrations. Lipid oxidation AUC was 1.3-fold higher significantly with H2-producing milk than with placebo consumption. Conclusively, activating intestinal bacterial H2 production by consuming a specific beverage may be a new strategy for promoting recovery and conditioning in athletes frequently performing intense exercises.
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Differential Effects of DPP-4 Inhibitors, Anagliptin and Sitagliptin, on PCSK9 Levels in Patients with Type 2 Diabetes Mellitus who are Receiving Statin Therapy.
Furuhashi, M, Sakuma, I, Morimoto, T, Higashiura, Y, Sakai, A, Matsumoto, M, Sakuma, M, Shimabukuro, M, Nomiyama, T, Arasaki, O, et al
Journal of atherosclerosis and thrombosis. 2022;(1):24-37
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Abstract
AIM: Proprotein convertase subtilisin/kexin type 9 (PCSK9) degrades the low-density lipoprotein (LDL) receptor, leading to hypercholesterolemia and cardiovascular risk. Treatment with a statin leads to a compensatory increase in circulating PCSK9 level. Anagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, was shown to decrease LDL cholesterol (LDL-C) levels to a greater extent than that by sitagliptin, another DPP-4 inhibitor, in the Randomized Evaluation of Anagliptin versus Sitagliptin On low-density lipoproteiN cholesterol in diabetes (REASON) trial. We investigated PCSK9 concentration in type 2 diabetes mellitus (T2DM) and the impact of treatment with anagliptin or sitagliptin on PCSK9 level as a sub-analysis of the REASON trial. METHODS PCSK9 concentration was measured at baseline and after 52 weeks of treatment with anagliptin (n=122) or sitagliptin (n=128) in patients with T2DM who were receiving statin therapy. All of the included patients had been treated with a DPP-4 inhibitor prior to randomization. RESULTS Baseline PCSK9 level was positively, but not significantly, correlated with LDL-C and was independently associated with platelet count and level of triglycerides. Concomitant with reduction of LDL-C, but not hemoglobin A1c (HbA1c), by anagliptin, PCSK9 level was significantly increased by treatment with sitagliptin (218±98 vs. 242±115 ng/mL, P=0.01), but not anagliptin (233±97 vs. 250±106 ng/mL, P=0.07). CONCLUSIONS PCSK9 level is independently associated with platelet count and level of triglycerides, but not LDL-C, in patients with T2DM. Anagliptin reduces LDL-C level independent of HbA1c control in patients with T2DM who are on statin therapy possibly by suppressing excess statin-mediated PCSK9 induction and subsequent degradation of the LDL receptor.