RESUMEN

Black soybean seed coat extract (BE) contains multiple bioactive polyphenols, including flavan-3-ols and anthocyanins. BE improves endothelial function; however, it is unclear whether BE protects endothelial cells from senescence. In this study, we examined the effects of BE on endothelial cell senescence and vascular function in healthy individuals. High concentrations of glucose were used to induce senescence in bovine aortic endothelial cells incubated with BE. Senescence, vascular function, and oxidative stress markers were measured. Incubation with BE remarkably inhibited senescence-associated ß-galactosidase and lactate dehydrogenase activities and dose dependently reduced intracellular reactive oxygen species levels in bovine aortic endothelial cells. BE treatment increased the levels of endothelial nitric oxide synthase (eNOS) mRNA and endothelial nitric oxide (NO) metabolites and increased the mRNA expression of klotho, a gene associated with an antiaging phenotype. To examine the effects of BE in humans, we conducted a clinical study using the second derivative of the fingertip photoplethysmogram to investigate vascular function and aging in 24 healthy volunteers. The participants consumed BE supplements (100 mg/day) or a placebo for 2 weeks. When compared with the placebo group, the BE group showed considerably improved vascular function, NO metabolite levels, and oxidative stress. These results suggest that BE supplementation improves endothelial function, possibly through antioxidant activity and NO production, and may consequently reduce the cardiovascular risk associated with aging. BE supplementation may be an effective and safe approach to reduce the risk of atherosclerosis and cardiovascular disease; however, additional studies investigating chronic vascular inflammation are needed.

Asunto(s)

RESUMEN

Soy protein has shown remarkable effectiveness in reducing fat mass compared with other protein sources, and exercise has the potential to further enhance this fat loss effect. Previous studies have demonstrated that soy protein intake leads to decreased fatty acid synthesis, which contributes to its fat-loss properties. However, the exact mechanism by which these lipids are consumed remains unclear. To investigate this, we conducted a comprehensive study using C57/BL6 male mice, comparing the effects of soy and casein proteins with and without exercise (Casein-Sed, Casein-Ex, Soy-Sed, and Soy-Ex groups) under high- and low-protein conditions (14% or 40% protein). Our findings revealed that combining soy protein intake with exercise significantly reduced epididymal white adipose tissue (eWAT) weight, particularly in the high-protein diet group. Further analysis revealed that exercise increased the expression of lipid oxidation-regulatory proteins, including mitochondrial oxidative phosphorylation protein (OXPHOS) complexes, in the plantaris muscle regardless of the protein source. Although soy protein intake did not directly affect muscle mitochondrial protein expression, the activity of OXPHOS complex I was additively enhanced by exercise and soy protein under the 40% protein condition. Notably, complex I activity inversely correlated with eWAT weight in the soy protein diet group. These results highlight the potential link between improved complex I activity induced by soy protein and fat mass reduction, which emphasizes the promising benefits of combining soy protein with exercise in promoting fat loss.NEW & NOTEWORTHY The findings revealed that soy protein intake combined with exercise resulted in reduced adipose tissue weight compared with that obtained with casein protein intake. Furthermore, the joint impact of exercise and soy protein consumption resulted in enhanced activity of oxidative phosphorylation protein (OXPHOS) complex I in fast-twitch muscles, which appears to be associated with fat mass reduction. These findings elucidate the potential additive effects of soy protein and exercise on body weight management.

Asunto(s)

RESUMEN

[Purpose] This study aimed to examine the validity and reproducibility of a new quantitative method for measuring spinal kyphosis using computed tomography (CT), and to investigate its relationship with reflux esophagitis. [Method] Using a new method to measure the index of kyphosis in CT images (IKCT), 10 examiners evaluated 10 cases of spinal kyphosis. One examiner measured 47 cases twice and 20 cases were examined to assess the validity with the kyphosis index. A case-control study was conducted on 303 cases of reflux esophagitis, of which 241 were mild and 62 severe. [Results] Regarding IKCT reproducibility, the inter-rater intraclass correlation coefficient was 0.977. The intra-rater intraclass correlation coefficient was 0.974. The correlation index with the kyphosis index was 0.731. A greater IKCT value, not contracting serious atrophic gastritis, and severe hiatal hernia were identified as risk factors for severe reflux esophagitis. [Conclusion] IKCT is a simple and useful method for measuring kyphosis. The prevention of kyphosis can help suppress severe reflux esophagitis.

Asunto(s)

RESUMEN

This study evaluated the effect of Lactococcus cremoris subsp. cremoris FC (FC) on constipation symptoms and the immune system in healthy participants with mild constipation. Eighty-three participants were randomised into four groups with different doses: 50, 75, and 100 mg of freeze-dried FC (test) or corn starch (placebo). Defaecation frequency significantly increased in all test groups compared to the placebo group. Stool appearance and volume were improved considerably within the groups administered 50 mg and 75 mg of FC. The abundances of total bacteria, Bifidobacterium spp., and Lactobacillus group in the faeces showed increasing trends in the test groups. Regarding immunological parameters, the naive T cell counts in the blood were significantly higher at a dose of 75 mg of FC in the test group than in the placebo group. These results suggest that FC intake improves defaecation and some immunological parameters, especially naive T cell counts, in healthy adults.

Asunto(s)

RESUMEN

An organoid is a three-dimensional (3D) in vitro cell culture emulating human organs. We applied 3D dynamic optical coherence tomography (DOCT) to visualize the intratissue and intracellular activities of human induced pluripotent stem cells (hiPSCs)-derived alveolar organoids in normal and fibrosis models. 3D DOCT data were acquired with an 840-nm spectral domain optical coherence tomography with axial and lateral resolutions of 3.8 µm (in tissue) and 4.9 µm, respectively. The DOCT images were obtained by the logarithmic-intensity-variance (LIV) algorithm, which is sensitive to the signal fluctuation magnitude. The LIV images revealed cystic structures surrounded by high-LIV borders and mesh-like structures with low LIV. The former may be alveoli with a highly dynamics epithelium, while the latter may be fibroblasts. The LIV images also demonstrated the abnormal repair of the alveolar epithelium.

RESUMEN

Bisphosphonates were introduced in the late 1990s to reduce the frequency of skeletal-related events(SREs)in patients with metastatic bone disease. In the 2010s, anti-RANKL antibodies were launched as another type of bone modifying agents(BMA). Both induce osteoclast apoptosis and have been used in Japan for solid tumors with bone metastases and multiple myeloma. In addition to osteoclasts, bone microenvironment includes a wide variety of cells such as osteoblasts, vascular endothelial cells, and immune cells, which spatiotemporally interact with cancer cells, resulting in the colonization of dissociated tumor cells(DTCs). Understanding the pathways and microenvironmental factors through which cancer evolves to promote bone colony formation will lead to better planning of the therapeutic strategies in individual cases and to further elucidation of molecular drivers.

Asunto(s)

RESUMEN

Deglutition aid foods are used to help patients with dysphagia take oral medications. Yoghurt is occasionally used to help swallow medications; however, its influence on pharmacokinetics is poorly understood. Yoghurt made with Lactococcus cremoris subsp. cremoris FC has a characteristic viscous texture that facilitates bolus formation and deglutition due to its metabolite exopolysaccharide. We assessed yoghurt prepared with L. cremoris FC as a food deglutition aid. We performed a dissolution test using famotidine powder mixed with yoghurt and a food thickener. Famotidine dissolution rates without deglutition-assisting foods and with yoghurt or food thickener were 102.3 ± 1.7, 85.7 ± 4.6, and 46.4 ± 1.1% after 15 min, respectively. Next, we orally administered famotidine powder with water, yoghurt, and food thickener to rats and measured plasma famotidine levels. We observed no significant differences between all test groups. The Tmax of famotidine mixed with a food thickener was significantly lower than that with yoghurt. These results suggest that yoghurt with L. cremoris FC did not remarkably affect the dissolution and pharmacokinetic profiles of famotidine powder. Thus, the administration of famotidine with yoghurt might be a suitable alternative to powder administration as a deglutition aid for patients.

Asunto(s)

RESUMEN

Cancer and cardiovascular disease share several risk factors. Clonal heamatopoiesis, a novel risk factor associated with both diseases, has received increasing attention in the fields of cardiology, heamatology and oncology. Clonal heamatopoiesis of indeterminate potential refers to the presence of at least one driver mutation in the heamatopoietic cells of peripheral blood without heamatological malignancy. Clonal heamatopoiesis of indeterminate potential is a common age-related condition that affects up to 60% of individuals aged > 80 years. Importantly, clonal heamatopoiesis of indeterminate potential carriers have a 2- to 4-fold higher risk of developing cardiovascular disease than non-carriers. Therefore, we performed an up-to-date review of clonal heamatopoiesis and its association with various forms of cardiovascular disease, including atherosclerotic disease, heart failure, aortic stenosis and pulmonary hypertension. In addition, we reviewed experimental studies that examined the causality and directionality between clonal heamatopoiesis and cardiovascular disease. Lastly, we discussed future research directions that will aid in the design of personalized therapies and preventive strategies for individuals with clonal heamatopoiesis. This review showed that clonal heamatopoiesis of indeterminate potential is a common condition, especially in older patients, and is associated with an increased risk of cardiovascular disease and worse prognosis. However, further research is needed to determine whether anti-inflammatory therapies or therapies that can reduce or eliminate clone size are effective in preventing cardiovascular disease in patients with clonal heamatopoiesis of indeterminate potential.

Asunto(s)

RESUMEN

Confirmation bias can impede accurate diagnosis. Since the approval of immune checkpoint inhibitors (ICIs), physicians are on high alert for newly developed immune-related adverse events (irAEs). Therefore, when patients present irAE-like symptoms, there is a risk of confirmation bias leading to overlooked diagnoses. This paper discusses a case of a patient with non-small cell lung cancer treated with nivolumab and topical dexamethasone ointment for an extended period due to oral mucocutaneous irAE. The patient developed adrenal insufficiency, initially considered to be a likely case of pituitary irAE. However, further investigation and the patient's clinical course revealed an unexpected diagnosis more in line with topical steroid withdrawal syndrome.

RESUMEN

Rationale: Although persistent fibroblast activation is a hallmark of idiopathic pulmonary fibrosis (IPF), mechanisms regulating persistent fibroblast activation in the lungs have not been fully elucidated. Objectives: On the basis of our observation that lung fibroblasts express TBXA2R (thromboxane-prostanoid receptor) during fibrosis, we investigated the role of TBXA2R signaling in fibrotic remodeling. Methods: We identified TBXA2R expression in lungs of patients with IPF and mice and studied primary mouse and human lung fibroblasts to determine the impact of TBXA2R signaling on fibroblast activation. We used TBXA2R-deficient mice and small-molecule inhibitors to investigate TBXA2R signaling in preclinical lung fibrosis models. Measurements and Main Results: TBXA2R expression was upregulated in fibroblasts in the lungs of patients with IPF and in mouse lungs during experimental lung fibrosis. Genetic deletion of TBXA2R, but not inhibition of thromboxane synthase, protected mice from bleomycin-induced lung fibrosis, thereby suggesting that an alternative ligand activates profibrotic TBXA2R signaling. In contrast to thromboxane, F2-isoprostanes, which are nonenzymatic products of arachidonic acid induced by reactive oxygen species, were persistently elevated during fibrosis. F2-isoprostanes induced TBXA2R signaling in fibroblasts and mediated a myofibroblast activation profile due, at least in part, to potentiation of TGF-ß (transforming growth factor-ß) signaling. In vivo treatment with the TBXA2R antagonist ifetroban reduced profibrotic signaling in the lungs, protected mice from lung fibrosis in three preclinical models (bleomycin, Hermansky-Pudlak mice, and radiation-induced fibrosis), and markedly enhanced fibrotic resolution after bleomycin treatment. Conclusions: TBXA2R links oxidative stress to fibroblast activation during lung fibrosis. TBXA2R antagonists could have utility in treating pulmonary fibrosis.

Asunto(s)

RESUMEN

Lactic acid bacteria are beneficial to Caenorhabditis elegans; however, bacteria acting as probiotics in nematodes may not necessarily have probiotic functions in humans. Lactococcus cremoris subsp. cremoris reportedly has probiotic functions in humans. Therefore, we determined whether the strain FC could exert probiotic effects in C. elegans in terms of improving host defenses and extending life span. Live FC successfully extended the life span and enhanced host defense compared to Escherichia coli OP50 (OP50), a standard food source for C. elegans. The FC-fed worms were tolerant to Salmonella enterica subsp. enterica serovar Enteritidis or Staphylococcus aureus infection and had better survival than the OP50-fed control worms. Further, the chemotaxis index, an indicator of perception ability, was more stable and significantly higher in FC-fed worms than in the control worms. The increase in autofluorescence from advanced glycation end products (AGEs) with aging was also ameliorated in FC-fed worms. FC showed beneficial effects in daf-16 and pmk-1 mutants, but not in skn-1 mutants. Since SKN-1 is the C. elegans ortholog of Nrf2, we measured the transcription of heme oxygenase-1 (HO-1), which is regulated by Nrf2, in murine macrophages and found that HO-1 mRNA expression was increased >5 times by inoculation with FC cells. Thus, FC could exert antisenescence effects via the SKN-1/Nrf2 pathway. This study showed for the first time that FC supported perceptive function and suppressed AGEs in nematodes as probiotic bacteria. Therefore, C. elegans can be an alternative model to screen for probiotic bacteria that can be used for antisenescence effects in humans. IMPORTANCE Aging is one of our greatest challenges. The World Health Organization proposed that "active aging" might encourage people to continue to work according to their capacities and preferences as they grow old and would prevent or delay disabilities and chronic diseases that are costly to both individuals and the society, considering that disease prevention is more economical than treatment. Probiotic bacteria, such as lactobacilli, are live microorganisms that exert beneficial effects on human health when ingested in sufficient amounts and can promote longevity. The significance of this study is that it revealed the antisenescence and various beneficial effects of the representative probiotic bacterium Lactococcus cremoris subsp. cremoris strain FC exerted via the SKN-1/Nrf2 pathway in the nematode Caenorhabditis elegans.

Asunto(s)

RESUMEN

Age-related muscle atrophy is associated with decreased protein anabolic capacity. Dietary intervention is an important strategy for the treatment of age-related muscle atrophy. This study examined the effect of Lactococcus cremoris subsp. cremoris FC-fermented milk on muscle mass and protein anabolic signaling in middle-aged mice. Male C57BL/6J mice (18-month-old) were divided into the control and Lactococcus cremoris subsp. cremoris FC-fermented milk supplementation groups. Mice were administered unfermented or fermented milk (300 µL/day) by gavage every alternate day for 8 weeks; thereafter, muscle weight, protein metabolic signaling factors, and inflammatory factors were investigated. Soleus muscle weight was higher in the fermented milk group than in the control group. Expression of insulin growth factor-1, a typical anabolic factor, and phosphorylation levels of anabolic signaling factors (mTOR and p70S6K) were higher after fermented milk supplementation. Levels of tumor necrosis factor-α, an inhibitor of protein anabolism, were lower in the fermented milk group. These data suggest that the daily intake of Lactococcus cremoris subsp. cremoris FC-fermented milk increased skeletal muscle mass as well as protein synthesis in the middle-aged mice, which may be mediated by reduction in the levels of inflammatory factors. Therefore, accelerated protein synthesis, induced by the consumption of fermented milk, has a potential role in counteracting muscle atrophy.

Asunto(s)

RESUMEN

Patients with dysphagia have difficulty swallowing oral medications. Swallowing aid foods, such as deglutition aid jellies and food thickeners, are often used to help such patients take oral medications. Yogurt is occasionally used to help swallow medications. It is also advantageous as it is nutritious and easy to swallow. However, the influence of yogurt on the pharmacokinetics of oral medications is poorly understood. In this study, we aimed to evaluate yogurt as a potential swallowing aid for the intake of oral tablets, by comparing the physical properties and effects of yogurt on disintegration and dissolution profiles of various oral tablets with deglutition aid jelly and xanthan gum-based food thickener. Yogurt and the food thickener were found to extend the disintegration time of several tablets; however, this increase was unremarkable. Although dissolution of magnesium oxide tablets decreased by 6%, 14%, and 25% after immersion in deglutition aid jelly, food thickener, and yogurt, respectively, at 15 min, this impact on dissolution reduced over time (dissolution rates of all samples at 120 min were over 90%). Rheological measurements showed that yogurt and food thickeners have a weak gel structure and therefore have better fluidity than deglutition aid jelly. The adhesiveness and dynamic viscosity of yogurt were higher than those of the food thickener, which delayed tablet disintegration and reduced the dissolution rate. However, these effects were not substantial. We can thus conclude that yogurt may be a useful swallowing aid for patients with deglutition disorders who take oral medications.

Asunto(s)

RESUMEN

Various dietary protein supplements are used by the elderly and bedridden to maintain their skeletal muscle mass and functions. High-quality proteins act as an anabolic driver and help to improve muscle strength and performance. Previously, we reported that soy protein significantly attenuates denervation-induced loss of muscle mass and myofiber cross sectional area in mice with inhibition of ubiquitination and degradation of IRS-1 in tibialis anterior muscle. It also increased muscle volume and strength in bedridden patients. In the present study, we investigated the effects of dietary soybean supplementation on muscle functions in taxi drivers lacking vigorous physical exercise. We conducted a case-control study on 25 healthy, male taxi drivers between the ages of 36 and 71 y performing minimal physical exercise. They were divided into two dietary groups: the soybean diet group (n=13) who ate daily meals (dinner) supplemented with 50 g of steamed soybean for 30 d and the control diet group (n=12) who received no soybean supplement. Next, we measured the muscle cross-sectional area (CSA) and muscle strength and function in both the groups before and after 30 d of soybean intake. The body weights of both diet groups did not differ significantly over time. However, after 30 d of soybean supplementation, the soybean-fed group developed significantly higher muscle CSA and grip strength compared to the control groups. In conclusion, dietary soybean supplementation improved muscle function in taxi drivers who lacked exercise.

Asunto(s)

RESUMEN

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is rapidly spreading worldwide, and the resultant disease, coronavirus disease (COVID-19), has become a global pandemic. Although there are multiple methods for detecting SARS-CoV-2, there are some issues with such tests, including long processing time, expense, low sensitivity, complexity, risk of contamination, and user friendly. This study evaluated the reproducibility and usability of a new point-of-care test (POCT) using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) for detecting SARS-CoV-2. METHODS: Samples from 96 patients with suspected SARS-CoV-2 infection were assessed using the real-time qRT-PCR-based POCT and the conventional real-time qRT-PCR method based on the Japanese National Institute of Infectious Diseases guidelines (registration number: jRCT1032200025). RESULTS: The real-time qRT-PCR-based POCT had a positive agreement rate of 90.0% (18/20), a negative agreement rate of 100% (76/76), and a total agreement rate of 97.9% (94/96), and the significantly high score of questionnaire survey (total score p < 0.0001). In the two cases in which real-time qRT-PCR-based POCT results did not match conventional real-time qRT-PCR test results, the SARS-CoV-2 RNA copy numbers were 8.0 copies per test in one case and below the detection limit in the other case when quantified using conventional real-time qRT-PCR. All patients could be triaged within 1 day using the real-time qRT-PCR-based POCT without invalid reports. CONCLUSIONS: The real-time qRT-PCR-based POCT not only had high reproducibility and useability but also allowed rapid patient triage. Therefore, it may be helpful in clinical settings.

Asunto(s)

RESUMEN

The appropriate diagnosis of carcinoma of unknown primary can be challenging for physicians, especially when they cannot apply a logical and ordered diagnostic process due to the unorthodox clinical characteristics. Here, we report the case of a 75-year-old woman presenting with multiple skeletal metastases with neither detectable visceral lesions nor site-specific distribution. Histological examination of a skeletal biopsy specimen unexpectedly revealed squamous cell carcinoma (SCC). Further specialized investigations led to the diagnosis of SCC of unknown primary. This case highlights the difficulty of the clinical differential diagnostic process in the quest for the occult primary tumor site.

RESUMEN

Strains of Lactococcus lactis subsp. cremoris are used to produce yogurt containing exopolysaccharides with a sticky texture. When strain G3-2 producing exopolysaccharides was grown at elevated temperatures, a spontaneous mutant EPSC, which had lost exopolysaccharides biosynthesis, was isolated. Genomes of the two strains were determined to be composed of a 2.4-Mb chromosome and up to eleven plasmids, and it was revealed that one of the plasmids encoding the gene cluster for exopolysaccharides biosynthesis was lost selectively in EPSC.

Asunto(s)

Asunto(s)

RESUMEN

The black yeast Aureobasidium pullulans produces abundant soluble ß-1,3-1,6-glucan-a functional food ingredient with known health benefits. For use as a food material, soluble ß-1,3-1,6-glucan is produced via fermentation using sucrose as the carbon source. Various functionalities of ß-1,3-1,6-glucan have been reported, including its immunomodulatory effect, particularly in the intestine. It also exhibits antitumor and antimetastatic effects, alleviates influenza and food allergies, and relieves stress. Moreover, it reduces the risk of lifestyle-related diseases by protecting the intestinal mucosa, reducing fat, lowering postprandial blood glucose, promoting bone health, and healing gastric ulcers. Furthermore, it induces heat shock protein 70. Clinical studies have reported the antiallergic and triglyceride-reducing effects of ß-1,3-1,6-glucan, which are indicators of improvement in lifestyle-related diseases. The primary and higher-order structures of ß-1,3-1,6-glucan have been elucidated. Specifically, it comprises a single highly-branched glucose residue with the ß-1,6 bond (70% or more) on a backbone of glucose with 1,3-ß bonds. ß-Glucan shows a triple helical structure, and studies on its use as a drug delivery system have been actively conducted. ß-Glucan in combination with anti-inflammatory substances or fullerenes can be used to target macrophages. Based on its health functionality, ß-1,3-1,6-glucan is an interesting material as both food and medicine.

Asunto(s)