Laboratory and clinical features of abnormal macroenzymes found in human sera.

We report the analysis of unusual macroenzymes, performed in our laboratory, and review the relevant literature. In particular, we focused on macro AST, macroamylase, macro LD and macro CK. Macroenzymes are seen in healthy subjects, but can also be related to disease; thus, accurate detection is useful in day-to-day clinical practice. The macroenzyme is thought to be a specific antigen-antibody complex from the following findings: (1) the complex could be dissociated under acidic pH levels; (2) binding specificity of immunoglobulin in the complex was observed; (3) the binding site of immunoglobulin in the complex was Fab portion; and (4) the maternal IgG involved with macroenzyme was transferred to her children. This article is part of a Special Issue entitled: Medical Proteomics.

Dietary inflammation, sleep and mental health in the United Kingdom and Japan: A comparative cross-sectional study.

Diet has been repeatedly shown to affect mental and sleep health outcomes. However, it is well known that there are cross-cultural differences in dietary practices as well as the prevalence of mental and sleep health outcomes. Given that the dietary inflammatory potential of diets has been linked to mental and sleep health outcomes, in the current study we sought to assess the inflammatory status of habitual diets and examine its relationship with mental and sleep health outcomes in both the United Kingdom and Japan. Our aim was to determine if the associations between the dietary inflammation index (DII) score and these health outcomes could elucidate any potential cross-cultural differences in health. Online survey data was collected from 602 participants (aged 18-40 years) in the United Kingdom (n = 288) and Japan (n = 314). Participants self-reported their dietary intakes, as well as current mental health and sleep patterns. The DII score was calculated (score range - 2.79 to 3.49) We found that although participants in the United Kingdom reported better overall mental wellbeing, participants in Japan reported less severe depression, anxiety and stress and better subjective sleep quality, less sleep disturbances and daytime dysfunction, despite sleeping shorter, and a better adherence to an anti-inflammatory diet. Moreover, across the United Kingdom and Japan, adherence to more anti-inflammatory diets predicted higher levels of subjective sleep quality, fewer sleep disturbances, less use of sleep medicine and less daytime dysfunction. In conclusion, there are several differences between mental and sleep health outcomes in the United Kingdom and Japan, which could be attributable to the inflammatory potential of respective regional diets. Future studies are warranted to examine the mental and sleep health benefits of adhering to anti-inflammatory traditional Japanese diets in clinical and subclinical cohorts.

Improvement of skin condition and intestinal microbiota via Heyndrickxia coagulans SANK70258 intake: A placebo-controlled, randomized, double-blind, parallel-group comparative study.

OBJECTIVE: Heyndrickxia coagulans SANK70258, a representative probiotic, is known for alleviating inflammation caused by cedar pollen, improving the intestinal environment and bowel movements. A previous study on consuming H. coagulans SANK70258 together with galactooligosaccharides showed a trend toward improvement in skin scaliness scores and subjective assessments of skin roughness. However, the effect of H. coagulans SANK70258 alone on the skin remains unclear. Thus, we aimed to re-evaluate the effects of the intake of H. coagulans SANK70258 alone on skin conditions and the intestinal environment through a clinical trial. METHODS: This placebo-controlled, double-blind clinical trial involved 80 Japanese women aged 30 to 65 with perceived skin roughness. Participants were divided into placebo and test groups. Over eight weeks, the test group consumed H. coagulans SANK70258, and its effects on skin condition and intestinal health were examined. RESULTS: The probiotic group showed significant intestinal improvements, with reduced fecal phenol levels (p = 0.044) and pH (p = 0.022), as well as enhanced skin lightness (L* value) (p = 0.040) and liver function tests. Metabolic analyses revealed decreases in fecal Nε-(carboxymethyl)lysine and plasma hydroxyproline, suggesting skin health benefits. There were also significant improvements in skin scaliness (p = 0.015) and bowel movement frequency (p = 0.032) in subgroup analysis. CONCLUSIONS: H. coagulans SANK70258 can improve skin health by improving the intestinal lining. This probiotic reduces the levels of intestinal putrefactive products and advanced glycation end-product levels in feces, suggesting that it may affect not only skin health but also systemic tissues such as the liver.

Development of an Evaluation System Using Intestinal Organoids for Drug Efflux Transport Analysis by an Imaging Approach.

There are several in vitro systems that enable evaluation of the absorption direction, but there are few quantitative systems that enable easy evaluation of the excretion direction. Enteroids, organoids derived from intestine, have been frozen and passaged for various research. But it is not clear how the freezing and passaging affect the expression and function of transporters. We investigated the effects of passage and cryopreservation of enteroids. We focused on P-gp (P-glycoprotein) and compared the transfer rates of rhodamine 123 (Rh123) into the lumen of enteroids with and without a P-gp inhibitor. mRNA expression levels did not change significantly before and after passage and cryopreservation. Accumulation of Rh123 in the lumen of enteroids was observed. With some P-gp inhibitors, excretion of Rh123 into the lumen of enteroids was inhibited and the nonexcreted Rh123 accumulated in enteroids epithelial cells. The transfer rate of Rh123 into the lumen of enteroids with a P-gp inhibitor was significantly decreased compared to that of without a P-gp inhibitor. Before and after passage and cryopreservation, the transfer rate was almost the same as that of primary cultured enteroids. We succeeded in easily evaluating whether a component is a substrate of P-gp using enteroids.

Effects of Prebiotic Yeast Mannan on Gut Health and Sleep Quality in Healthy Adults: A Randomized, Double-Blind, Placebo-Controlled Study.

Human gut health is closely related to sleep. We aimed to evaluate the efficacy of yeast mannan (YM) in improving bowel habits and sleep quality, along with metabolomics in fecal samples. A total of 40 healthy adults (age range, 22-64 years) with discomfort in defecation were enrolled and randomly allocated to receive either YM (n = 20; 1.1 g/day) or placebo (n = 20) for four weeks. Participants recorded their defecation habits throughout the test periods. Sleep electroencephalogram (EEG) recording using an EEG device and fecal sampling were performed pre- and post-treatment. The YM group significantly increased defecation frequency and stool volumes compared to the placebo group. After 4 weeks of treatment, the non-REM sleep stage 3 (N3) duration in the YM group was significantly higher than that in the placebo group. YM ingestion significantly lengthened total time in bed (TIB) and significantly shortened N3 latency compared to placebo intake during the trial. The metabolomics analysis found a total of 20 metabolite differences between the YM and placebo groups. As a result of stepwise linear regression, changes in fecal propionate and gamma-aminobutyric acid (GABA) levels were identified as the primary factors explaining changes in TIB and N3 latency, respectively. Our findings suggest that the prebiotic YM could be beneficial to gut health and sleep quality.

Brain-derived neurotrophic factor induces angiogenin secretion and nuclear translocation in human umbilical vein endothelial cells.

Brain-derived neurotrophic factor (BDNF) is a well-known humoral protein that induces growth of neurons. Recent studies have suggested that BDNF could act as an angiogenesis inducer similar to vascular endothelial growth factor (VEGF). Angiogenin is a strong mediator of angiogenesis. It has particular characteristics both as a secreted protein and a transcription factor. After being incorporated into the cytoplasm, angiogenin is immediately transferred to the nucleus and then mediates the angiogenic effects of angiogenesis inducers, including VEGF. The aim of this study is to determine the association between BDNF and angiogenin. At first, we determined the secretion of angiogenin from human umbilical vein endothelial cells (HUVEC) induced by BDNF with enzyme-linked immunosorbent assay. Next, we determined BDNF-induced nuclear translocation of angiogenin by immunofluorescent staining. In addition, we examined the mRNA expression of angiogenin in HUVEC before and after BDNF stimulation by quantitative reverse transcriptase-polymerase chain reaction. As a result, we noted that BDNF induced angiogenin secretion and nuclear translocation without an increase in the mRNA expression in HUVEC. Furthermore, we demonstrated that BDNF-induced HUVEC proliferation was significantly suppressed when neomycin, a specific inhibitor of nuclear translocation of angiogenin, was administered. These findings indicate that nuclear translocation of angiogenin is critically involved in BDNF-induced proliferation of HUVEC. In conclusion, angiogenin contributes to angiogenesis induced by BDNF.

Apoptosis-associated tyrosine kinase is a Cdk5 activator p35 binding protein.

A 3(')-terminal fragment of a splice variant of KIAA0641, a human homologue of apoptosis-associated tyrosine kinase (AATYK), was screened from human brain cDNA libraries by a yeast two-hybrid system using a Cdk5 activator p35 as a bait. The cloned cDNA encoded 477 amino acids, composed of internal 458 amino acids of KIAA0641 and 19 amino acids unique to this variant after splicing, then referred to this clone as hAATYKs-p35BP (human AATYK short isoform-p35 binding polypeptide). Using GST-fusion protein, hAATYKs-p35BP was shown to bind to Cdk5/p35 in a rat brain extract. hAATYKs made by fusing the kinase domain of KIAA0641 to the N-terminus of hAATYKs-p35BP was used for binding to Cdk5/p35 in HEK293 cells. Both hAATYKs and KIAA0641 bound to and were phosphorylated by Cdk5/p35. These results suggest that both isoforms of hAATYK are novel Cdk5/p35-binding and substrate proteins.