-
1.
Conserved cysteine residues in Kaposi's sarcoma herpesvirus ORF34 are necessary for viral production and viral pre-initiation complex formation.
Watanabe, T, Narahari, A, Bhardwaj, E, Kuriyama, K, Nishimura, M, Izumi, T, Fujimuro, M, Ohno, S
bioRxiv : the preprint server for biology. 2023
Abstract
Kaposi's sarcoma herpesvirus (KSHV) ORF34 is a component of the viral pre-initiation complex (vPIC), a highly conserved piece of machinery essential for late gene expression among beta- and gamma-herpes viruses. KSHV ORF34 is also estimated to be a hub protein, associated with the majority of vPIC components. However, the precise mechanisms underlying how the ORF34 molecule contributes to the vPIC function, including the binding manner to other vPIC components, remain unclear. Therefore, we constructed ORF34 alanine-scanning mutants, in which amino-acid residues that were conserved among other herpesviruses had been replaced by alanine. The mutants were analyzed for their binding functions to other vPIC factors, and then were evaluated for their recovering ability of viral production using the cells harboring ORF34-deficient KSHV-BAC. The results demonstrated that at least four cysteines conserved in ORF34 were crucial for binding to other vPIC components, ORF24 and ORF66, virus production, and late gene transcription and expression. Based on the amino acid sequence of ORF34, these four cysteines were expected to constitute a pair of C-Xn-C consensus motifs. An artificial intelligence-predicted structure model revealed that the four cysteines were present tetrahedrally in an intramolecular fashion. Another prediction algorithm indicated the possible capture of metal cations by ORF34. Furthermore, it was experimentally observed that the elimination of cations by a selective chelator resulted in the loss of ORF34's binding ability to other vPIC components. In conclusion, our results suggest the functional importance of KSHV ORF34 conserved cysteines for vPIC components assembly and viral replication.
-
2.
Oral Iron Absorption of Ferric Citrate Hydrate and Hepcidin-25 in Hemodialysis Patients: A Prospective, Multicenter, Observational Riona-Oral Iron Absorption Trial.
Tomosugi, N, Koshino, Y, Ogawa, C, Maeda, K, Shimada, N, Tomita, K, Daimon, S, Shikano, T, Ryu, K, Takatani, T, et al
International journal of molecular sciences. 2023;(18)
Abstract
Oral ferric citrate hydrate (FCH) is effective for iron deficiencies in hemodialysis patients; however, how iron balance in the body affects iron absorption in the intestinal tract remains unclear. This prospective observational study (Riona-Oral Iron Absorption Trial, R-OIAT, UMIN 000031406) was conducted at 42 hemodialysis centers in Japan, wherein 268 hemodialysis patients without inflammation were enrolled and treated with a fixed amount of FCH for 6 months. We assessed the predictive value of hepcidin-25 for iron absorption and iron shift between ferritin (FTN) and red blood cells (RBCs) following FCH therapy. Serum iron changes at 2 h (ΔFe2h) after FCH ingestion were evaluated as iron absorption. The primary outcome was the quantitative delineation of iron variables with respect to ΔFe2h, and the secondary outcome was the description of the predictors of the body's iron balance. Generalized estimating equations (GEEs) were used to identify the determinants of iron absorption during each phase of FCH treatment. ΔFe2h increased when hepcidin-25 and TSAT decreased (-0.459, -0.643 to -0.276, p = 0.000; -0.648, -1.099 to -0.197, p = 0.005, respectively) in GEEs. FTN increased when RBCs decreased (-1.392, -1.749 to -1.035, p = 0.000) and hepcidin-25 increased (0.297, 0.239 to 0.355, p = 0.000). Limiting erythropoiesis to maintain hemoglobin levels induces RBC reduction in hemodialysis patients, resulting in increased hepcidin-25 and FTN levels. Hepcidin-25 production may prompt an iron shift from RBC iron to FTN iron, inhibiting iron absorption even with continued FCH intake.
-
3.
Association between Levocarnitine Treatment and the Change in Knee Extensor Strength in Patients Undergoing Hemodialysis: A Post-Hoc Analysis of the Osaka Dialysis Complication Study (ODCS).
Matsufuji, S, Shoji, T, Lee, S, Yamaguchi, M, Nishimura, M, Tsujimoto, Y, Nakatani, S, Morioka, T, Mori, K, Emoto, M
Nutrients. 2022;(2)
Abstract
Carnitine deficiency is prevalent in patients undergoing hemodialysis, and it could result in lowered muscle strength. So far, the effect of treatment with levocarnitine on lower limb muscle strength has not been well described. This observational study examined the association between treatment with levocarnitine with the change in knee extensor strength (KES) in hemodialysis patients. Eligible patients were selected from the participants enrolled in a prospective cohort study for whom muscle strength was measured annually. We identified 104 eligible patients for this analysis. During the one-year period between 2014 to 2015, 67 patients were treated with intravenous levocarnitine (1000 mg per shot, thrice weekly), whereas 37 patients were not. The change in KES was significantly higher (p = 0.01) in the carnitine group [0.02 (0.01-0.04) kgf/kg] as compared to the non-carnitine group [-0.02 (-0.04 to 0.01) kgf/kg]. Multivariable-adjusted regression analysis showed the positive association between the change in KES and the treatment with levocarnitine remained significant after adjustment for the baseline KES and other potential confounders. Thus, treatment with intravenous levocarnitine was independently and positively associated with the change in KES among hemodialysis patients. Further clinical trials are needed to provide more solid evidence.
-
4.
Randomized trial of an intensified, multifactorial intervention in patients with advanced-stage diabetic kidney disease: Diabetic Nephropathy Remission and Regression Team Trial in Japan (DNETT-Japan).
Shikata, K, Haneda, M, Ninomiya, T, Koya, D, Suzuki, Y, Suzuki, D, Ishida, H, Akai, H, Tomino, Y, Uzu, T, et al
Journal of diabetes investigation. 2021;(2):207-216
Abstract
AIMS/INTRODUCTION We evaluated the efficacy of multifactorial intensive treatment (IT) on renal outcomes in patients with type 2 diabetes and advanced-stage diabetic kidney disease (DKD). MATERIALS AND METHODS The Diabetic Nephropathy Remission and Regression Team Trial in Japan (DNETT-Japan) is a multicenter, open-label, randomized controlled trial with a 5-year follow-up period. We randomly assigned 164 patients with advanced-stage diabetic kidney disease (urinary albumin-to-creatinine ratio ≥300 mg/g creatinine, serum creatinine level 1.2-2.5 mg/dL in men and 1.0-2.5 mg/dL in women) to receive either IT or conventional treatment. The primary composite outcome was end-stage kidney failure, doubling of serum creatinine or death from any cause, which was assessed in the intention-to-treat population. RESULTS The IT tended to reduce the risk of primary end-points as compared with conventional treatment, but the difference between treatment groups did not reach the statistically significant level (hazard ratio 0.69, 95% confidence interval 0.43-1.11; P = 0.13). Meanwhile, the decrease in serum low-density lipoprotein cholesterol level and the use of statin were significantly associated with the decrease in primary outcome (hazard ratio 1.14; 95% confidence interval 1.05-1.23, P < 0.001 and hazard ratio 0.53, 95% confidence interval 0.28-0.998, P < 0.05, respectively). The incidence of adverse events was not different between treatment groups. CONCLUSIONS The risk of kidney events tended to decrease by IT, although it was not statistically significant. Lipid control using statin was associated with a lower risk of adverse kidney events. Further follow-up study might show the effect of IT in patients with advanced diabetic kidney disease.
-
5.
Pathology definitions and resection strategies for early colorectal neoplasia: Eastern versus Western approaches in the post-Vienna era.
Nishimura, M, Saito, Y, Nakanishi, Y, Shia, J, Lauwers, GY, Wallace, MB
Gastrointestinal endoscopy. 2020;(5):983-988
Abstract
There is a well-known discrepancy between East and West classifications of colorectal neoplasm, especially "intramucosal carcinoma," categorized as subgroup 4.4 in the Vienna classification, usually recognized as high-grade dysplasia in the United States and as carcinoma in situ in Japan. Focusing on management, in the current National Comprehensive Cancer Network algorithm, high-grade dysplasia, carcinoma in situ, and intramucosal carcinoma are managed similarly, whereas submucosal invasion by carcinoma requires en bloc resection. To bridge the differences with regard to these conceptual problems in the definition and management of carcinoma in situ and intramucosal carcinoma, endoscopists and pathologists from Japan and the United States gathered and discussed from their perspectives how to accurately assess specimens of en bloc/piecemeal resection and to effectively predict lymph node metastasis risk.
-
6.
Effect of Electrical Muscle Stimulation on Upper and Lower Limb Muscles in Critically Ill Patients: A Two-Center Randomized Controlled Trial.
Nakanishi, N, Oto, J, Tsutsumi, R, Yamamoto, T, Ueno, Y, Nakataki, E, Itagaki, T, Sakaue, H, Nishimura, M
Critical care medicine. 2020;(11):e997-e1003
Abstract
OBJECTIVES Electrical muscle stimulation is widely used to enhance lower limb mobilization. Although upper limb muscle atrophy is common in critically ill patients, electrical muscle stimulation application for the upper limbs has been rarely reported. The purpose of this study was to investigate whether electrical muscle stimulation prevents upper and lower limb muscle atrophy and improves physical function. DESIGN Randomized controlled trial. SETTING Two-center, mixed medical/surgical ICU. PATIENTS Adult patients who were expected to be mechanically ventilated for greater than 48 hours and stay in the ICU for greater than 5 days. INTERVENTIONS Forty-two patients were randomly assigned to the electrical muscle stimulation (n = 17) or control group (n = 19). MEASUREMENTS AND MAIN RESULTS Primary outcomes were change in muscle thickness and cross-sectional area of the biceps brachii and rectus femoris from day 1 to 5. Secondary outcomes included occurrence of ICU-acquired weakness, ICU mobility scale, length of hospitalization, and amino acid levels. The change in biceps brachii muscle thickness was -1.9% versus -11.2% in the electrical muscle stimulation and control (p = 0.007) groups, and the change in cross-sectional area was -2.7% versus -10.0% (p = 0.03). The change in rectus femoris muscle thickness was -0.9% versus -14.7% (p = 0.003) and cross-sectional area was -1.7% versus -10.4% (p = 0.04). No significant difference was found in ICU-acquired weakness (13% vs 40%; p = 0.20) and ICU mobility scale (3 vs 2; p = 0.42) between the groups. The length of hospitalization was shorter in the electrical muscle stimulation group (23 d [19-34 d] vs 40 d [26-64 d]) (p = 0.04). On day 3, the change in the branched-chain amino acid level was lower in the electrical muscle stimulation group (40.5% vs 71.5%; p = 0.04). CONCLUSIONS In critically ill patients, electrical muscle stimulation prevented upper and lower limb muscle atrophy and attenuated proteolysis and decreased the length of hospitalization.
-
7.
Effects of Vibrotactile Feedback on Sedentary Behaviors in Adults: A Pilot Randomized Controlled Trial.
Nishimura, M, Sasai, H, Nakata, Y, Maeda, S
International journal of environmental research and public health. 2019;(23)
Abstract
No effective and easily implemented intervention strategies for reducing sedentary behavior have been established. This pilot trial (UMIN000024372) investigated whether vibrotactile feedback reduces sedentary behavior. Twenty-six adults aged 30-69 years who were sedentary ≥8 h/day were randomly assigned to control (n = 13) or vibration (n = 13) groups. Participants wore a monitor 9 h daily for seven-day periods at baseline (week zero), during the intervention (weeks one, three, five, and seven), and after the intervention (week eight). During the eight-week intervention, vibration-group participants were notified by a vibration through the monitor whenever continuous sedentary time reached ≥30 min; they also received weekly reports of their sedentary patterns. Control-group participants did not receive feedback. The primary outcome was change in total sedentary time. Changes in longer bouts of sedentary time (≥35 min) were also assessed. No significant difference was found in the change in total sedentary time (control: -17.5 min/9 h, vibration: -9.1 min/9 h; p = 0.42). Although no significant differences were observed in sedentary time in longer bouts, vibration-group participants exhibited significantly lower sedentary time (-21.6 min/9 h, p = 0.045). Thus, vibration feedback does not appear to offer any advantages in reducing total sedentary time.
-
8.
Daily Ingestion of Eggplant Powder Improves Blood Pressure and Psychological State in Stressed Individuals: A Randomized Placebo-Controlled Study.
Nishimura, M, Suzuki, M, Takahashi, R, Yamaguchi, S, Tsubaki, K, Fujita, T, Nishihira, J, Nakamura, K
Nutrients. 2019;11(11)
-
-
-
Free full text
Plain language summary
Prevention and management of hypertension are major public health challenges worldwide. Psychosocial factors are related to blood pressure and may lead to hypertension. The aim of this study was to examine the long-term antihypertensive, anti-stress, and psychological state-improving effects of eggplant in human participants with normal-high blood pressure and grade 1 hypertension. The study is a randomized, double-blind, placebo-controlled, parallel-group comparative study. The participants were randomized into one of two intervention groups; placebo group or eggplant group. The participants ingested four eggplant powder capsules, or four placebo capsules every day for 12 weeks. Results indicate that continuous intake of eggplant powder improved blood pressure in participants with normal-high blood pressure and grade 1 hypertension. Additionally, eggplant intake improved positive and negative psychosocial states. Authors conclude that eggplant should be utilised as a safe treatment for blood pressure and mental health.
Abstract
Eggplant (Solanum melongena) is a globally popular vegetable and its significant health effect has not been reported in randomized controlled trials. Recently, we reported that eggplant was rich in choline esters, including acetylcholine (ACh), and had an antihypertensive effect in spontaneously hypertensive rats. Here, we evaluated the effects of a continuous intake of eggplant powder on blood pressure (BP), stress, and psychological state (PS) in 100 stressed participants with normal-high BP or grade 1 hypertension in a randomized, double-blind, placebo-controlled, parallel-group comparative study. The participants were randomly assigned to the eggplant or placebo group. Participants in the eggplant group ingested capsules containing eggplant powder (1.2 g/day; 2.3 mg of ACh/day) for 12 weeks, whereas participants in the placebo group ingested placebo capsules. The primary outcome assessed was hospital BP. Secondary outcomes were stress and PS. Eggplant powder intake significantly decreased the hospital diastolic blood pressure (DBP) at week 8 overall and in the normal-high BP group, and the systolic blood pressure (SBP) and DBP at week 12 overall and in the grade 1 hypertension group, compared to those of the placebo group. It also improved negative PSs at week 8 or 12 in the normal-high BP group. This is the first evidence of the BP- and PS-improving effects of eggplant intake in humans. The functional substance responsible for the effects was estimated to be eggplant-derived choline ester, namely ACh.
-
9.
Effect of Daily Ingestion of Quercetin-Rich Onion Powder for 12 Weeks on Visceral Fat: A Randomised, Double-Blind, Placebo-Controlled, Parallel-Group Study.
Nishimura, M, Muro, T, Kobori, M, Nishihira, J
Nutrients. 2019;(1)
Abstract
Quercetin, which is frequently found in vegetables such as onion, is widely found to have biological activities such as visceral fat reduction. Therefore, we performed this randomised double-blind placebo-controlled parallel-group study and analysed the effects of daily intake of quercetin-rich onion on visceral fat for 12 weeks. Seventy healthy Japanese subjects whose body mass index (BMI) was ≥23 and <30 were recruited and randomly assigned to either the quercetin-rich onion group or placebo group. The subjects ingested 9 g of onion powder per day for 12 weeks. We conducted medical interviews, hematological and biological tests; measured body composition and vital signs; and analysed the Food Frequency Questionnaire weeks 0, 4, 8, and 12. Abdominal fat area was measured using computed tomography scanning at weeks 0 and 12. No significant differences in visceral fat area (VFA) were observed between the two groups. However, in subjects whose high-density lipoprotein cholesterol was lower, VFA was significantly lower in the quercetin-rich onion group. In addition, alanine aminotransferase was significantly lower in the quercetin-rich onion group than in the placebo group. Thus, the results suggest that quercetin-rich onion may be beneficial for preventing obesity and improving liver function.
-
10.
Influence of Nutritional Management and Rehabilitation on Physical Outcome in Japanese Intensive Care Unit Patients: A Multicenter Observational Study.
Yatabe, T, Egi, M, Sakaguchi, M, Ito, T, Inagaki, N, Kato, H, Kaminohara, J, Konishi, A, Takahashi, M, Tatsumi, H, et al
Annals of nutrition & metabolism. 2019;(1):35-43
Abstract
BACKGROUND There is lack of evidence regarding nutritional management among intensive care unit (ICU) patients in a population with relatively low body mass index. Therefore, we conducted an observational study to assess the nutritional management in Japanese ICUs. Also, we investigated the impact of nutritional management and rehabilitation on physical outcome. METHODS The study population comprised 389 consecutive patients who received mechanical ventilation for at least 24 h and those admitted to the ICU for > 72 h in 13 hospitals. The primary outcomes were caloric and protein intake in ICU on days 3 and 7, and at ICU discharge. The secondary outcome was the impact of nutritional management and rehabilitation on physical status at ICU discharge. We defined good physical status as more than end sitting and poor physical status as bed rest and sitting. We divided the participants into 2 groups, namely, the good physical status group (Good group) and poor physical status group (Poor group) for analysis of the secondary outcome. Data were expressed as median (interquartile range). RESULTS The median amount of caloric intake on days 3 and 7, and at ICU discharge via enteral and parenteral routes were 8.4 (3.1-15.6), 14.9 (7.5-22.0), and 11.2 (2.5-19.1) kcal/kg/day, respectively. The median amount of protein intake on days 3 and 7, and at ICU discharge were 0.2 (0-0.5), 0.4 (0.1-0.8), and 0.3 (0-0.7) g/kg/day, respectively. The amount of caloric intake on day 3 in the Poor group was significantly higher than that of the Good group (10.1 [5.8, 16.2] vs. 5.2 [1.9, 12.4] kcal/kg/day, p < 0.001). The proportion of patients who were received rehabilitation in ICU in the Good group was significantly higher than that of the Poor group (92 vs. 63%, p < 0.001). The multivariate analysis revealed that caloric intake on day 3 and rehabilitation in ICU were considered independent factors that affect physical status (OR 1.19; 95% CI 1.05-1.34; p = 0.005 and OR 0.07; 95% CI 0.01-0.34; p = 0.001). CONCLUSIONS The caloric and protein intakes in Japanese ICUs were 15 kcal/kg/day and 0.4 g/kg/day, respectively. In addition, critically ill patients might benefit from low caloric intake (less than 10 kcal/kg/day) until day 3 and rehabilitation during ICU stay.