Environment-friendly utilization of squid pen with water: Production of β-chitin nanofibers and peptides for lowering blood pressure

Chitin, an abundant biopolymer on Earth, represents a resource for sustainable functional materials. However, traditional β-chitin production methods involve alkaline treatment at approximately 90 °C for its separation from the protein, thus not suitable as a functional peptide, as it is mixed with an alkaline aqueous solution. This study examined the conversion of squid pen into solid β-chitin and water-soluble peptides using only water at temperatures of 150–250 °C for 30–120 min. Solid β-chitin was converted to its nanofiber form and the physicochemical properties of the β-chitin nanofibers were almost the same as those produced by the traditional method. Because this method uses only water, the protein in the squid pen may also be a functional peptide for lowering blood pressure, by inhibiting the Angiotensin-1 converting enzyme. High-temperature water treatment is a promising environment-friendly technique for complete utilization of squid pen components, including β-chitin and protein.ArticleInternational Journal of Biological Macromolecules.189:921-929(2021)journal articl

Iron Chelation Therapy with Deferasirox Results in Improvement of Liver Enzyme Level in Patients with Iron Overload-Associated Liver Dysfunction

Iron chelation therapy (ICT) has been applied for the patients with iron overload-associated liver dysfunction since it is one of the causes of death in patients with intractable hematological diseases requiring multiple red blood cell transfusions. Recently, deferasirox (DSX), a novel, once-daily oral iron chelator, was demonstrated to have similar efficacy to the conventional continuous infusion of deferoxamine on a decrease in serum ferritin (SF) level in heavily transfused patients. We show three cases of transfusion-mediated iron-overloaded patients with an elevated serum alanine aminotransaminase (ALT). All three patients who received the ICT with DSX showed a decrease in ALT level in association with a decrease in SF level. It is suggested that DSX therapy could be considered to expect the improvement of liver damage for iron-overloaded patients with an abnormal ALT level

Validity of a Risk Prediction Equation for CKD After 10 Years of Follow-up in a Japanese Population: The Ibaraki Prefectural Health Study

BACKGROUND:Chronic kidney disease (CKD) is an important health problem for which risk equations have been developed for Western populations. This study aimed to develop and validate a risk prediction equation for CKD in a Japanese population.STUDY DESIGN:Observational cohort study.SETTING & PARTICIPANTS:The study included 135,007 participants who completed an annual health checkup in 1993 to 1996 in the Ibaraki Prefecture in Japan. Participants were initially free of CKD (defined as stage 3, 4, or 5 CKD or proteinuria [2+ or 3+] by dipstick). Follow-up information was available from health checkups 10 years after the initial evaluation. We used data from 40,963 women and 17,892 men in the northern region of the prefecture for the development of risk prediction equations and 53,042 women and 23,110 men in the southern region for external validation.PREDICTORS:Age, estimated glomerular filtration rate (eGFR), body mass index, proteinuria, hematuria, hypertension, diabetes mellitus, smoking, and drinking.OUTCOME:Occurrence of CKD (defined as eGFR0.8 for both the development and external validation populations, and discrimination of the risk estimation was fairly good in women and men.LIMITATIONS:Fluctuations in variables were not evaluated because the study used annual health checkups. This study excluded a large number of people for whom a 10-year health checkup was not available.CONCLUSIONS:Estimations of risk for CKD after 10 years of follow-up in a general Japanese population can be achieved with a high level of validity

Impact and attribute of each obesity-related cardiovascular risk factor in combination with abdominal obesity on total health expenditures in adult Japanese National Health insurance beneficiaries: The Ibaraki Prefectural health study.

The aim of this study was to examine the attribution of each cardiovascular risk factor in combination with abdominal obesity (AO) on Japanese health expenditures.The health insurance claims of 43,469 National Health Insurance beneficiaries aged 40-75 years in Ibaraki, Japan, from the second cohort of the Ibaraki Prefectural Health Study were followed-up from 2009 through 2013. Multivariable health expenditure ratios (HERs) of diabetes mellitus (DM), high low-density lipoprotein cholesterol (LDL-C), low high-density lipoprotein cholesterol (HDL-C), and hypertension with and without AO were calculated with reference to no risk factors using a Tweedie regression model.Without AO, HERs were 1.58 for DM, 1.06 for high LDL-C, 1.27 for low HDL-C, and 1.31 for hypertension (all P < 0.05). With AO, HERs were 1.15 for AO, 1.42 for DM, 1.03 for high LDL-C, 1.11 for low HDL-C, and 1.26 for hypertension (all P < 0.05, except high LDL-C). Without AO, population attributable fractions (PAFs) were 2.8% for DM, 0.8% for high LDL-C, 0.7% for low HDL-C, and 6.5% for hypertension. With AO, PAFs were 1.0% for AO, 2.3% for DM, 0.4% for low HDL-C, and 5.0% for hypertension.Of the obesity-related cardiovascular risk factors, hypertension, independent of AO, appears to impose the greatest burden on Japanese health expenditures

Effect of purification method of β-chitin from squid pen on the properties of β-chitin nanofibers

Published online 20 June 2016The relationship between purification methods of β-chitin from squid pen and the physicochemical properties of β-chitin nanofibers (NFs) were investigated. Two types of β-chitin were prepared, with β-chitin (a → b) subjected to acid treatment for decalcification and then base treatment for deproteinization, while β-chitin (b → a) was treated in the opposite order. These β-chitins were disintegrated into NFs using wet pulverization. The β-chitin (b → a) NF dispersion has higher transmittance and viscosity than the β-chitin (a → b) NF dispersion. For the first time, we succeeded in obtaining 3D images of the β-chitin NF dispersion in water by using quick-freeze deep-etch replication with high-angle annular dark field scanning transmission electron microscopy. The β-chitin (b → a) NF dispersion has a denser and more uniform 3D network structure than the β-chitin (a → b) NF dispersion. Widths of the β-chitin (a → b) and (b → a) NFs were approximately 8–25 and 3–10 nm, respectively.ArticleINTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES. 91:987-993 (2016)journal articl

Postazacitidine clone size predicts long-term outcome of patients with myelodysplastic syndromes and related myeloid neoplasms

Azacitidine is a mainstay of therapy for MDS-related diseases. The purpose of our study is to elucidate the effect of gene mutations on hematological response and overall survival (OS), particularly focusing on their post-treatment clone size. We enrolled a total of 449 patients with MDS or related myeloid neoplasms. They were analyzed for gene mutations in pre- (n=449) and post- (n=289) treatment bone marrow samples using targeted-capture sequencing to assess the impact of gene mutations and their post-treatment clone size on treatment outcomes. In Cox proportional hazard modeling, multi-hit TP53 mutation (HR, 2.03; 95% CI, 1.42-2.91; P<.001), EZH2 mutation (HR, 1.71; 95% CI, 1.14-2.54; P=.009), and DDX41 mutations (HR, 0.33; 95% CI, 0.17-0.62; P<.001), together with age, high-risk karyotypes, low platelet, and high blast counts, independently predicted OS. Post-treatment clone size accounting for all drivers significantly correlated with International Working Group (IWG)-response (P<.001, trend test), except for that of DDX41-mutated clones, which did not predict IWG-response. Combined, IWG-response and post-treatment clone size further improved the prediction of the original model and even that of a recently proposed molecular prediction model, IPSS-M (c-index, 0.653 vs 0.688; P<.001, likelihood ratio test). In conclusion, evaluation of post-treatment clone size, together with pre-treatment mutational profile as well as IWG-response have a role in better prognostication of azacitidine-treated myelodysplasia patients

Bortezomib-cyclophosphamide-dexamethasone induction/consolidation and bortezomib maintenance for transplant-eligible newly diagnosed multiple myeloma: phase 2 multicenter trial

[Objectives:] We conducted a phase II trial to prospectively evaluate the efficacy and safety of bortezomib-cyclophosphamide-dexamethasone (VCD) induction, autologous stem cell transplantation (ASCT), VCD consolidation, and bortezomib maintenance in transplant-eligible newly diagnosed multiple myeloma (NDMM) patients in Japan (UMIN000010542). [Methods:] From 2013 to 2016, 42 patients with a median age of 58 (range 42–65) years with NDMM were enrolled in 15 centers. The primary endpoint was the complete response (CR) /stringent CR (sCR) rate after transplantation, and overall/progression-free survival rates were also evaluated. [Results:] Following induction therapy, the overall response rate was obtained in 71% of patients, including a CR/sCR of 10% and a very good partial response (VGPR) of 26%. Twenty-six of the 42 patients completed ASCT following the protocol and CR/sCR and VGPR rate 100 days after ASCT was 26% and 17%, respectively. During consolidation therapy, 3 of the 24 patients achieved deeper responses. Eight of the 18 patients completed 2-year bortezomib maintenance without disease progression and grade 3/4 toxicities. Five patients were VGPR or partial response after ASCT but maintained response with 2-year bortezomib maintenance. Two-year overall and progression-free survival rates were 92.5% (95% confidence interval [CI]: 78.5%−97.5%) and 62.6% (95% CI: 45.8%−75.5%), respectively. Grade 3/4 toxicities (≥ 10%) included neutropenia (19%) and anemia (17%) in induction, and thrombocytopenia (29%) in consolidation. [Conclusion:] VCD induction/consolidation and bortezomib maintenance with ASCT for NDMM resulted in a high CR/sCR rate and provided good overall/progression-free survival in Japan

Development of Risk Prediction Equations for Incident Chronic Kidney Disease

IMPORTANCE ‐ Early identification of individuals at elevated risk of developing chronic kidney disease  could improve clinical care through enhanced surveillance and better management of underlying health  conditions.  OBJECTIVE – To develop assessment tools to identify individuals at increased risk of chronic kidney  disease, defined by reduced estimated glomerular filtration rate (eGFR).  DESIGN, SETTING, AND PARTICIPANTS – Individual level data analysis of 34 multinational cohorts from  the CKD Prognosis Consortium including 5,222,711 individuals from 28 countries. Data were collected  from April, 1970 through January, 2017. A two‐stage analysis was performed, with each study first  analyzed individually and summarized overall using a weighted average. Since clinical variables were  often differentially available by diabetes status, models were developed separately within participants  with diabetes and without diabetes. Discrimination and calibration were also tested in 9 external  cohorts (N=2,253,540). EXPOSURE Demographic and clinical factors.  MAIN OUTCOMES AND MEASURES – Incident eGFR <60 ml/min/1.73 m2.  RESULTS – In 4,441,084 participants without diabetes (mean age, 54 years, 38% female), there were  660,856 incident cases of reduced eGFR during a mean follow‐up of 4.2 years. In 781,627 participants  with diabetes (mean age, 62 years, 13% female), there were 313,646 incident cases during a mean follow‐up of 3.9 years. Equations for the 5‐year risk of reduced eGFR included age, sex, ethnicity, eGFR, history of cardiovascular disease, ever smoker, hypertension, BMI, and albuminuria. For participants  with diabetes, the models also included diabetes medications, hemoglobin A1c, and the interaction  between the two. The risk equations had a median C statistic for the 5‐year predicted probability of  0.845 (25th – 75th percentile, 0.789‐0.890) in the cohorts without diabetes and 0.801 (25th – 75th percentile, 0.750‐0.819) in the cohorts with diabetes. Calibration analysis showed that 9 out of 13 (69%) study populations had a slope of observed to predicted risk between 0.80 and 1.25. Discrimination was  similar in 18 study populations in 9 external validation cohorts; calibration showed that 16 out of 18 (89%) had a slope of observed to predicted risk between 0.80 and 1.25. CONCLUSIONS AND RELEVANCE – Equations for predicting risk of incident chronic kidney disease developed in over 5 million people from 34 multinational cohorts demonstrated high discrimination and  variable calibration in diverse populations

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京都大学0048新制・課程博士博士(医学)甲第11060号医博第2773号新制||医||875(附属図書館)22592UT51-2004-J732京都大学大学院医学研究科内科系専攻(主査)教授 前川 平, 教授 米原 伸, 教授 内山 卓学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDA