Comprehensive Dipeptide Analysis Revealed Cancer-Specific Profile in the Liver of Patients with Hepatocellular Carcinoma and Hepatitis

As the physical properties and functionality of dipeptides differ from those of amino acids, they have attracted attention in metabolomics; however, their functions in vivo have not been clarified in detail. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, and its major cause is chronic hepatitis. This study was conducted to explore tumor-specific dipeptide characteristics by performing comprehensive dipeptide analysis in the tumor and surrounding nontumor tissue of patients with HCC. Dipeptides were analyzed by liquid chromatography tandem mass spectrometry and capillary electrophoresis tandem mass spectrometry. Principal component analysis using 236 detected dipeptides showed differences in the dipeptide profiles between nontumor and tumor tissues; however, no clear difference was observed in etiological comparison. In addition, the N- and C-terminal amino acid compositions of the detected dipeptides significantly differed, suggesting the substrate specificity of enzyme proteins, such as peptidase. Furthermore, hepatitis-derived HCC may show a characteristic dipeptide profile even before tumor formation. These results provide insight into HCC pathogenesis and may help identify novel biomarkers for diagnosis

Belt Electrode-Skeletal Muscle Electrical Stimulation in Older Hemodialysis Patients with Reduced Physical Activity: A Randomized Controlled Pilot Study

Background: Although patients receiving hemodialysis are more likely to develop metabolic disorders and muscle weakness at an earlier stage than healthy individuals, many older dialysis patients have difficulty establishing exercise habits to prevent these problems. Therefore, we evaluated the use of belt electrode-skeletal muscle electrical stimulation (B-SES), which can stimulate a wider area than conventional electrical muscle stimulation (EMS), to examine its application and safety in older hemodialysis patients as a means to improve lower extremity function without voluntary effort. Methods: This study was a randomized controlled trial (RCT) involving 20 older dialysis patients (>65 years old) with reduced physical activity. The control group received 12 weeks of routine care only and the intervention group received 12 weeks of B-SES during hemodialysis in addition to routine care. The primary endpoint was the 6 min walk test (6MWT) distance, while the Short Physical Performance Battery (SPPB), body composition, Functional Independence Measure (FIM), biochemistry test, and blood pressure/pulse measurements were used as secondary endpoints. Results: As a result of the 12-week B-SES intervention, no increase in creatine kinase or C-reactive protein levels was observed after the intervention in either group, and no adverse events attributed to the B-SES intervention were observed in the intervention group. Furthermore, the intervention group showed a significant improvement in the 6MWT and SPPB scores after the intervention. Conclusions: The results of this study suggest that a 12-week B-SES intervention during hemodialysis sessions safely improves 6MWT distance and SPPB scores in older patients with a reduced level of physical activity

A Metabolomic Profile Predictive of New Osteoporosis or Sarcopenia Development

The increasing number of patients with osteoporosis and sarcopenia is a global concern among countries with progressively aging societies. The high medical costs of treating those patients suggest that prevention rather than treatment is preferable. We enrolled 729 subjects who attended both the second and third surveys of the Research on Osteoarthritis/Osteoporosis Against Disability (ROAD) study. Blood samples were collected from subjects at the second survey, and then a comprehensive metabolomic analysis was performed. It was found that 35 had newly developed osteoporosis at the third survey performed four years later, and 39 were newly diagnosed with sarcopenia at the third survey. In the second survey, we found that serum Gly levels were significantly higher even after adjustment for age, sex, and BMI in subjects with newly developed osteoporosis relative to those who remained osteoporosis-negative during the four-year follow-up. We also show that serum taurine levels were significantly lower at the second survey, even after adjustment for age, sex, and BMI in subjects with newly developed sarcopenia during the four-year follow-up compared with those not diagnosed with sarcopenia at the second or third surveys. Though our sample size and odds ratios were small, increased Gly and decreased taurine levels were found to be predictive of new development of osteoporosis and sarcopenia, respectively, within four years

Comparative analysis of cerebrospinal fluid metabolites in Alzheimer’s disease and idiopathic normal pressure hydrocephalus in a Japanese cohort

Abstract Background Alzheimer’s disease (AD) is a most common dementia in elderly people. Since AD symptoms resemble those of other neurodegenerative diseases, including idiopathic normal pressure hydrocephalus (iNPH), it is difficult to distinguish AD from iNPH for a precise and early diagnosis. iNPH is caused by the accumulation of cerebrospinal fluid (CSF) and involves gait disturbance, urinary incontinence, and dementia. iNPH is treatable with shunt operation which removes accumulated CSF from the brain ventricles. Methods We performed metabolomic analysis in the CSF of patients with AD and iNPH with capillary electrophoresis-mass spectrometry. We assessed metabolites to discriminate between AD and iNPH with Welch’s t-test, receiver operating characteristic (ROC) curve analysis, and multiple logistic regression analysis. Results We found significant increased levels of glycerate and N-acetylneuraminate and significant decreased levels of serine and 2-hydroxybutyrate in the CSF of patients with AD compared to the CSF of patients with iNPH. The ROC curve analysis with these four metabolites showed that the area under the ROC curve was 0.90, indicating good discrimination between AD and iNPH. Conclusions This study identified four metabolites that could possibly discriminate between AD and iNPH, which previous research has shown are closely related to the risk factors, pathogenesis, and symptoms of AD. Analyzing pathway-specific metabolites in the CSF of patients with AD may further elucidate the mechanism and pathogenesis of AD