Improved Sendai viral system for reprogramming to naive pluripotency

優れた多分化能を持つヒトのナイーブ型iPS細胞を迅速に作製する方法を発明. 京都大学プレスリリース. 2022-10-18.A novel method for generating naive human iPS cells with significantly higher differentiation potency. 京都大学プレスリリース. 2022-11-15.Naive human induced pluripotent stem cells (iPSCs) can be generated by reprogramming somatic cells with Sendai virus (SeV) vectors. However, only dermal fibroblasts have been successfully reprogrammed this way, and the process requires culture on feeder cells. Moreover, SeV vectors are highly persistent and inhibit subsequent differentiation of iPSCs. Here, we report a modified SeV vector system to generate transgene-free naive human iPSCs with superior differentiation potential. The modified method can be applied not only to fibroblasts but also to other somatic cell types. SeV vectors disappear quickly at early passages, and this approach enables the generation of naive iPSCs in a feeder-free culture. The naive iPSCs generated by this method show better differentiation to trilineage and extra-embryonic trophectoderm than those derived by conventional methods. This method can expand the application of iPSCs to research on early human development and regenerative medicine

The Tokyo Oldest Old Survey on Total Health (TOOTH): A longitudinal cohort study of multidimensional components of health and well-being

<p>Abstract</p> <p>Background</p> <p>With the rapid worldwide increase in the oldest old population, considerable concern has arisen about the social and economic burden of diseases and disability in this age group. Understanding of multidimensional structure of health and its life-course trajectory is an essential prerequisite for effective health care delivery. Therefore, we organized an interdisciplinary research team consisting of geriatricians, dentists, psychologists, sociologists, and epidemiologists to conduct a longitudinal observational study.</p> <p>Methods/Design</p> <p>For the Tokyo Oldest Old Survey on Total Health (TOOTH) study, a random sample of inhabitants of the city of Tokyo, aged 85 years or older, was drawn from the basic city registry. The baseline comprehensive assessment consists of an in-home interview, a self-administered questionnaire, and a medical/dental examination. To perform a wide variety of biomedical measurements, including carotid ultrasonography and a detailed dental examination, participants were invited to our study center at Keio University Hospital. For those who were not able to visit the study center, we provided the option of a home-based examination, in which participants were simultaneously visited by a geriatrician and a dentist. Of 2875 eligible individuals, a total of 1152 people were recruited, of which 542 completed both the in-home interview and the medical/dental examination, with 442 completed the in-home interview only, and another 168 completed self or proxy-administered data collection only. Carotid ultrasonography was completed in 458 subjects, which was 99.6% of the clinic visitors (n = 460). Masticatory assessment using a colour-changeable chewing gum was completed in 421 subjects, a 91.5% of the clinic visitors.</p> <p>Discussion</p> <p>Our results demonstrated the feasibility of a new comprehensive study that incorporated non-invasive measurements of subclinical diseases and a detailed dental examination aiming at community-dwelling individuals aged 85 years or older. The bimodal recruitment strategy is critically important to capture a broad range of health profiles among the oldest old. Results form the TOOTH study will help develop new models of health promotion, which are expected to contribute to an improvement in lifelong health and well-being.</p> <p>Trial Registration</p> <p>This study has been registered in the UMIN-Clinical Trial Registry (CTR), ID: UMIN000001842.</p

Long-chain monounsaturated fatty acids improve endothelial function with altering microbial flora

Fish oil-derived long-chain monounsaturated fatty acids (LCMUFAs) with a carbon chain length longer than 18 units ameliorate cardiovascular risk in mice. In this study, we investigated whether LCMUFAs could improve endothelial functions in mice and humans. In a double-blind, randomized, placebo-controlled, parallel-group, multi-center study, healthy subjects were randomly assigned to either an LCMUFA oil (saury oil) or a control oil (olive and tuna oils) group. Sixty subjects were enrolled and administrated each oil for 4 weeks. For the animal study, ApoE−/− mice were fed a Western diet supplemented with 3% of either gadoleic acid (C20:1) or cetoleic acid (C22:1) for 12 weeks. Participants from the LCMUFA group showed improvements in endothelial function and a lower trimethylamine-N-oxide level, which is a predictor of coronary artery disease. C20:1 and C22:1 oils significantly improved atherosclerotic lesions and plasma levels of several inflammatory cytokines, including IL-6 and TNF-α. These beneficial effects were consistent with an improvement in the gut microbiota environment, as evident from the decreased ratio of Firmicutes and/ or Bacteroidetes, increase in the abundance of Akkermansia, and upregulation of short-chain fatty acid (SCFA)-induced glucagon-like peptide-1 (GLP-1) expression and serum GLP-1 level. These data suggest that LCMUFAs alter the microbiota environment that stimulate the production of SCFAs, resulting in the induction of GLP-1 secretion. Fish oil-derived long-chain monounsaturated fatty acids might thus help to protect against cardiovascular disease

オカラがラットの血漿・肝臓脂質およびアディポサイトカイン濃度に及ぼす影響

effects of okara on plasma lipid，liver lipid and adipocytokine levels in rats were investigated to clarify that okara would be suitable as a material for a functional food. When okara was given to rats fed a high-cholesterol diet，the increase in plasma cholesterol level and the decrease in plasma adiponectin level were suppressed. The improvement of the levels of serum cholesterol and adipocytokine induced by the intake of okara suggests that okara would be useful for prevention of lifestyle-related diseases

新規乳酸菌を用いたおから・豆乳発酵食品の成分特性

Soybean is widely used in Japanese dietary pattern. Okara is a by-product generated mainly during processing of soybean. A great deal of okara has been treated as industrial waste. A lot of soy proteins which are functional components are included in okara. We have proposed a beneficial use for okara. Yoghurt-like food used in this experiment was prepared from a mixture of okara and soymilk by lactic acid fermentation. We investigated nutritional and food characteristics of this yoghurt-like food and obtained following results. Soy proteins in okara and soymilk were scarcely digested during the fermentation. Some soy proteins have been known to exhibit cholesterol-lowering effect. In the yoghurt-like food lactic acid occurred predominantly among several organic acids detected by HPLC. An improvement effect on enteric environment was expected because stachyose could not be degraded by lactic acid fermentation and it would be used by other microorganisms in intestine. The difference of isoflavone content between the unfermented food and yoghurt-like food was not observed. Soy isoflavones remained without degradation during lactic acid fermentation. These results suggested that the intake of yoghurt-like soy food would improve serum cholesterol concentration and intestinal environment

大豆乳酸発酵食品がラットの血漿および肝臓脂質濃度に及ぼす影響

Yogurt-like food (Soy-Yogurt) was prepared by lactic fermentation of okara and soybean milk which suppress the increase of blood lipid level. To investigate the effect of Soy-Yogurt on the lipid metabolism in rat, male Sprague-Dawley rats were fed a high-cholesterol diet for 8 weeks. A control group was fed a diet containing 1% cholesterol, while the other two groups were fed the diets which were replaced with freeze-dried Soy-Yogurt either 10% or 20%, respectively. The increases of body weight and total cholesterol level in plasma of 20% Soy-Yogurt group were significantly suppressed compared to those of the control group, respectively. The twenty percentage Soy-Yogurt group maintained a high level of plasma adiponectin. The levels of hepatic total lipid, cholesterol and triglyceride were significantly decreased with the increase of Soy-Yogurt content in the feed. These results suggest that the ingestion of Soy-Yogurt improves the lipid metabolism in rats fed a high-cholesterol diet

オカラ豆乳の乳酸発酵処理がラットの脂質代謝に及ぼす影響

This study examined the effects of fermented soymilk and okara on lipid metabolism in rats. Fermented soymilk and okara was prepared from a mixture of soymilk and okara blended in a ratio of 2 to 1 on dry basis by lactic acid fermentation using Lactobacillus delbrueckii. Male Sprague-Dawley rats were fed a diet based on the AIN-93 diet（ control diet） or two kinds of test diets in which 20% of a control diet was replaced by unfermented soymilk/okara mixture or fermented soymilk/okara for 7 weeks. We investigated changes in plasma and hepatic lipid levels of rats, and the regulation of gene expression in mesenteric adipose tissue and liver by DNA microarray. Groups of test diet significantly reduced plasma cholesterol levels compared with the control diet. In addition, the hepatic triglyceride in rats fed test diets was significantly lower than that of control diet. DNA microarray analysis indicated that the test diet ingestion down-regulated the expression of genes related to lipid metabolism in mesenteric adipose tissue and liver. These results suggested that a mixture of soymilk and okara has the effect improving lipid metabolism. Especially, fermented soymilk and okara seems to promote the restraint of abdominal visceral fat accumulation in comparison with unfermented soymilk and okara. Therefore, fermented soymilk and okara is a functional food showing effect preventing metabolic syndrome

ラット脂質代謝に影響を及ぼす豆乳の有効濃度について

It is known that soy protein has the hypolipidemic action on blood and liver. We investigated to clarify physiologically effective concentration of soymilk. Male Sprague-Dawley rats aged 7weeks were fed a control die（t AIN-93G, soy protein free）, or a test diet in which 10.78%（corresponding to soy protein 5%）or 21.55%（corresponding to soy protein 10%）of the diet was replaced with soymilk, respectively. The rats were fed the control diet or the test diet for 5weeks. The administration of soymilk significantly suppressed total cholesterol level in plasma and decreased liver lipid and visceral fat. These effects depended on the concentration of administrated soymilk. It was suggested that soymilk improved the lipid metabolism in rat. Moreover, it was found that the administration of amount of soymilk corresponding to more than 10% soy protein was necessary to obtain a significant physiological effect in a short period