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Concentration-dependence of specific rotation of optically active glycerol analogues and structurally related compounds : The significance of intermolecular hydrogen bonding
Get PDFSpecific rotation of optically active glycerol analogues, (S)-3-(benzyloxy)propane-1,2-diol [(S)-1], (S)-3-methoxypropane-1,2-diol [(S)-6] and (S)-3-phenoxypropane-1,2-diol [(S)-13], changed its sign from (+) to (–) with increasing concentration in CHCl3, whereas no significant concentration-dependent change was observed in MeOH. The 1H NMR spectrum of (S)-1 showed concentration-dependent changes of the chemical shift in CDCl3. Intermolecular interaction by OH⋯OH hydrogen bonds was suggested by single crystal X-ray crystallography of (S)-13. The concentration-dependent changes of specific rotation of (S)-1, (S)-6, and (S)-13 in CHCl3 can therefore be presumed to be due to self-assembly of these compounds via intermolecular hydrogen bonding at high concentration. The remarkable concentration-dependent changes in specific rotation were also observed to occur in the compounds with related chemical structures, such as (S)-3-hydroxy-4-methoxy-4-oxobutanoic acid [(S)-10], (S)-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid [Boc-L-Pro-OH, (S)-14], (R)-3-hydroxy-4,4-dimethylhydrofran-2(3H)-one [(R)-15], (R)-tetrahydrofuran-2-carboxylic acid [(R)-16], (S)-3-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoic acid [Boc-L-Val-OH, (S)-17], (R)-oxiran-2-ylmethanol [(R)-18], and (4S)-4-isopropyloxazolidin-2-one [(S)-19]. The existence of intermolecular interaction by C=O⋯HO hydrogen bonds was suggested by single crystal X-ray crystallography of (S)-10, (S)-13, and (S)-14. Thus, this series of chiral compounds have multiple functional groups in appropriate positions that serve as hydrogen-bond donors and/or acceptors, resulting in significant concentration-dependent changes of specific rotation.journal articl
ビタミンDの代謝調節と体内時計の関与について
Get PDFIn chronic renal failure patients and dialysis patients, hyperphosphatemia and hypovitaminosis occur due to impaired urinary phosphorus excretion and vitamin D activation, leading to secondary hyperparathyroidism and renal osteodystrophy.These events can lead to severe ectopic calcification in blood vessels and the heart, increasing the risk of cardiovascular disease and death.In recent years, approximately half of patients undergoing dialysis have diabetes, so it is important to prevent the progression to diabetic nephropathy as one of the three major complications. Furthermore, it has been reported that hyperphosphatemia increases the risk of developing heart failure and death even when renal function is normal, and blood concentrations of phosphorus and 1，25（OH）2D, the active form of vitamin D, have a circadian rhythm. Therefore, quantitative, qualitative, and temporal nutritional management of dietary phosphorus during a wide range of life stages from healthy to disease is important for maintaining homeostasis of vitamin D, calcium, and bone metabolism, and for preventing the onset and progression of kidney disease, not only is it useful, but it is also thought to be useful in preventing lifestyle-related diseases such as diabetes and inflammatory diseases from becoming more severe. In this article, we will discuss vitamin D deficiency/insufficiency in renal disease, its relationship with circadian rhythms, energy and cholesterol metabolism revealed through research on the regulation of vitamin D metabolism, differences in phosphorus sensitivity at life stages.journal articl
生命金属元素鉄の新たな役割と治療応用
Get PDFIron is the most abundant trace metal and indispensable for the biogenicity of living organisms. Iron deficiency anemia is often observed in iron-related disorders, and therefore, proactive iron intake is recommended. In contrast, iron causes oxidative stress by catalyzing the Fenton reaction. Recent evidence suggests that iron is involved in the pathophysiology of non-iron-accumulating diseases, and the role of iron has been revisited. In the last three decades, many studies have shown that iron content is associated with diabetes and that high iron intake increases the risk of diabetes onset. Iron reduction by phlebotomy or iron chelators ameliorates insulin sensitivity and secretion. Several studies have shown that high iron levels are also associated with obesity. Therefore, we speculate that iron reduction could exert a favorable effect on obesity. As expected, iron chelators mitigated obesity by inhibiting inflammatory cytokines and oxidative stress in KKAy mice. We advocate that “iron stress” is related to iron-dependent inflammation and oxidative stress, and have reported that iron stress is involved in kidney disease, sarcopenia, vascular dysfunction, and so on. However, non-specific iron reduction always causes iron-deficient adverse effects, such as anemia, and it is difficult to adopt a clinical application. Macrophage plays a critical role in chronic inflammation including obesity and diabetes. M1 inflammatory macrophages exhibit an iron-retention phenotype with elevated H-ferritin（ FTH） expression. Mice with macrophage-specific FTH deletion（FTHKO） showed reduced iron concentrations in macrophages, without anemia. HFD- induced obesity and diabetes were alleviated in FTHKO mice by inhibiting inflammation and oxidative stress in adipose tissue, similar to the effect of systemic iron reduction. Therefore, macrophages are the main source of iron stress, leading to new therapeutic strategies for controlling the iron levels in macrophages.journal articl
遺伝性乳がん卵巣がん症候群に対するリスク低減卵巣卵管摘出術への意思決定に関する海外の動向
Get PDFHereditary breast and ovarian cancer syndrome（HBOC） has been reported to account for about 10-15％ of all ovarian cancers, and risk-reducing salpingo-oophorectomy（RRSO） is regarded as the only preventive measure against the risk of such cancers. It is important for patients with BRCA 1/2 pathogenic variants to undergo RRSO after childbearing, between the ages of 35 to 45, but a multifaceted perspective is needed when considering this procedure, as it may cause physical and psychological problems. This paper discusses factors that influence decision-making regarding RRSO from three perspectives : demographics, medical history, and psychosociology, with reference to previous studies. Accurate insight into the background that led to the decision to undergo RRSO is crucial for support. Above all, it is essential to utilize such insight in healthcare as vital information to prevent death from breast or ovarian cancer among HBOC patients.journal articl
Synthesis of secretory leukocyte protease inhibitor using cell-free protein synthesis system
Get PDFSecretory leukocyte protease inhibitor (SLPI) functions as a protease inhibitor that modulates excessive proteolysis in the body, exhibits broad-spectrum antimicrobial activity, regulates inflammatory responses, and plays an important role in the innate immunity. The purpose of the study was to artificially synthesize a SLPI, an antimicrobial peptide, and investigate its effect on antimicrobial activity against Porphyromonas gingivalis and interleukin-6 (IL-6) production. SLPI protein with a molecular weight of approximately 13 kDa was artificially synthesized using a cell-free protein synthesis (CFPS) system and investigated by western blotting and enzyme-linked immunosorbent assay (ELISA). Disulfide bond isomerase in the protein synthesis mixture increased the amount of SLPI synthesized. The synthesized SLPI (sSLPI) protein was purified and its antimicrobial activity was investigated based on the growth of Porphyromonas gingivalis and bacterial adhesion to oral epithelial cells. The effect of sSLPI on IL-6 production in human periodontal ligament fibroblasts (HPLFs) was examined by ELISA. Our results showed that sSLPI significantly inhibited the growth of Porphyromonas gingivalis and bacterial adhesion to oral epithelial cells and further inhibited IL-6 production by HPLFs. These results suggested that SLPI artificially synthesized using the CFPS system may play a role in the prevention of periodontal diseases through its antimicrobial and anti-inflammatory effects.journal articl
徳島県立海部病院における医療格差是正と医師働き方改革のための遠隔医療 : 遠隔救急診療と5G遠隔診療
Get PDFFor local government hospitals in sparsely populated areas, access to emergency and specialized medical care is essential for the wellbeing of local residents. However, Tokushima Prefectural Kaifu Hospital has grappled with numerous crises in the past, stemming from a chronic shortage of doctors. Due to the inherent challenges and constraints associated with traditional face-to-face medical treatment, where doctors directly provide medical care, it becomes challenging to ensure the sustainability of emergency and specialized medical care with limited staffing. To address this issue, we are opting for a paradigm shift in medical care driven by digital technology, often referred to as Digital Transformation（DX）. At our hospital, we introduced a remote emergency medical treatment system for emergency medical care in 2013 and for remote outpatient treatment in 2018 as part of medical DX. The former is a system that transmits medical images taken at a hospital to a smartphone or tablet to support on-call doctors and foster collaboration between hospitals. Under remote outpatient treatment, specialists from remote medical institutions deliver medical care to patients visiting our hospital; this service has been harnessing 5G connectivity in recent years. By embracing medical DX, we not only ensured the quality of medical care but also reduced the mental and physical strain on doctors and patients. This enabled medical institutions in depopulated areas to provide sustainable emergency and specialized medical care. If implemented, these measures may contribute toward rectifying the medical disparities between urban and depopulated areas.journal articl
BMI and Cardiometabolic Traits in Japanese : A Mendelian Randomization Study
Get PDFBackground: Although many observational studies have demonstrated significant relationships between obesity and cardiometabolic traits, the causality of these relationships in East Asians remains to be elucidated.
Methods: We conducted individual-level Mendelian randomization (MR) analyses targeting 14,083 participants in the Japan Multi-Institutional Collaborative Cohort Study and two-sample MR analyses using summary statistics based on genome-wide association study data from 173,430 Japanese. Using 83 body mass index (BMI)-related loci, genetic risk scores (GRS) for BMI were calculated, and the effects of BMI on cardiometabolic traits were examined for individual-level MR analyses using the two-stage least squares estimator method. The β-coefficients and standard errors for the per-allele association of each single-nucleotide polymorphism as well as all outcomes, or odds ratios with 95% confidence intervals were calculated in the two-sample MR analyses.
Results: In individual-level MR analyses, the GRS of BMI was not significantly associated with any cardiometabolic traits. In two-sample MR analyses, higher BMI was associated with increased risks of higher blood pressure, triglycerides, and uric acid, as well as lower high-density-lipoprotein cholesterol and eGFR. The associations of BMI with type 2 diabetes in two-sample MR analyses were inconsistent using different methods, including the directions.
Conclusion: The results of this study suggest that, even among the Japanese, an East Asian population with low levels of obesity, higher BMI could be causally associated with the development of a variety of cardiometabolic traits. Causality in those associations should be clarified in future studies with larger populations, especially those of BMI with type 2 diabetes.journal articl
The effects of pyrroloquinoline quinone disodium salt on brain function and physiological processes
Get PDFPyrroloquinoline quinone disodium salt (PQQ) is a red trihydrate crystal that was approved as a new food ingredient by FDA in 2008. Now, it is approved as a food in Japan and the EU. PQQ has redox properties and exerts antioxidant, neuroprotective, and mitochondrial biogenesis effects. The baseline intake level of PQQ is considered to be 20 mg / day. PQQ ingestion lowers blood lipid peroxide levels in humans, suggesting antioxidant activity. In the field of cognitive function, double-blind, placebo-controlled trials have been conducted. Various improvements have been reported regarding general memory, verbal memory, working memory, and attention. Furthermore, a stratified analysis of a population with a wide range of ages revealed unique effects in young people (20–40 years old) that were not observed in older adults (41–65 years old). Specifically, cognitive flexibility and executive speed improved more rapidly in young people at 8 weeks. Co-administration of PQQ and coenzyme Q10 further enhanced these effects. In an open-label trial, PQQ was shown to improve sleep and mood. Additionally, PQQ was found to suppress skin moisture loss and increase PGC-1α expression. Overall, PQQ is a food with various functions, including brain health benefits.journal articl