Ubiquinol-10 Intake Is Effective in Relieving Mild Fatigue in Healthy Individuals

Our double-blind, placebo-controlled study evaluated effects of ubiquinol, the reduced form of coenzyme Q10, on mild fatigue in healthy individuals experiencing fatigue in daily life that had continued for more than 1 and less than 6 months. The participants received 100-mg/day (Ubq100; age 44.0 ± 9.8 years; 14 females and 6 males) or 150-mg/day ubiquinol (Ubq150; age 40.4 ± 11.8 years; 14 females and 8 males) or placebo (Plc; age 41.3 ± 13.4 years; 13 females and 7 males) daily for 12 weeks. Measurements of subjective and objective fatigue were conducted by using questionnaires-based fatigue scales/visual analogue scales and autonomic nerve function/biological oxidation index, respectively, prior to the first dosing and every 4 weeks thereafter. Serum ubiquinol level increased three- to four-fold after 4 weeks and remained significantly higher than that after Plc administration throughout the intake period. Although a higher blood level of ubiquinol was observed with Ubq150 than with Ubq100, the difference was not statistically significant. In both Ubq100 and Ubq150 groups, subjective levels of fatigue sensation and sleepiness after cognitive tasks, which consisted of the modified Advanced Trail Making Test, the modified Stroop Color-Word Test, and the Digit Symbol Substitution Test, improved significantly compared with those in the placebo group, suggesting an anti-fatigue effect. The Ubq150 group demonstrated significant improvement compared with the Plc group regarding subjective level of relaxation after task, sleepiness before and after task, motivation for task, and serum level of oxidative stress. Correlation analysis between blood level of ubiquinol and each evaluated effect suggested a positive relationship with relaxation after task, motivation for cognitive task, and parasympathetic activity. The results of the study suggest that ubiquinol intake relieves mild fatigue in healthy individuals

Analysis of the mechanism by which BALB/c mice having prior immunization with nucleocapsid protein of SARS-CoV develop severe pneumonia after SARS-CoV infection

AbstractThe precise mechanism of severe acute respiratory syndrome (SARS), which is caused by SARS-associated coronavirus (SARS-CoV), is still unclear. We generated recombinant vaccinia virus (rVV) LC16m8 strain which simultaneously expresses four structural proteins of SARS-CoV, including nucleocapsid (N), membrane (M), envelop (E), spike (S) proteins (rVV-NMES) and reported that old BALB/c mice having prior immunization with rVV-NMES develop severe pneumonia similar to those of control mice though rVV-NMES-immunized mice showed lower pulmonary viral titer than in the control mice. Furthermore, we determined which SARS-CoV structural protein for the prior rVV-immunization is responsible for the severe pneumonia after the SARS-CoV infection as observed in the rVV-NMES-immunized mice. Old BALB/c mice were inoculated intradermally with rVV that expressed each structural proteins of SARS-CoV (rVV-N, -M, -E, or -S) with or without rVV-S and then infected intranasally with SARS-CoV more than 4 weeks later. At 9 days after SARS-CoV infection, the rVV-N-immunized mice show more severe pneumonia than in other groups. Furthermore, significant up-regulation of Th1 (IL-2)- and Th2 (IL-4 and IL-5)-bias cytokines and down-regulation of anti-inflammatory cytokine (IL-10 and TGF-β) were observed in rVV-N-immunized mice, resulting in the intensive infiltration of immunocompetent cells into the lung. In contrast, rVV-S-immunized mice showed only low pulmonary viral tier and slight pneumonia. However, the mice having co-immunization with both rVV-N and rVV-S showed severe pneumonia though their pulmonary viral titer was low. These results suggest that an excessive host immune response against the N protein of SARS-CoV is involved in severe pneumonia caused by SARS-CoV infection. These findings increase our understanding of the pathogenesis of SARS

The effects of dark chocolate on cognitive performance during cognitively demanding tasks: A randomized, single-blinded, crossover, dose-comparison study

Dark chocolate, rich in polyphenols, increases cerebral blood flow and improves cognitive function. This study aimed to determine whether the consumption of chocolate with a high concentration of polyphenols helps to maintain cognitive performance during cognitively demanding tasks. In this randomized, single-blinded, crossover, dose-comparison study, 18 middle-aged adults consumed two types of chocolate (25 g each), one with a high concentration (635.0 mg) and the other with a low concentration (211.7 mg) of cacao polyphenols, and performed a cognitive task requiring response inhibition and selective attention over two time periods (15–30 min and 40–55 min after consumption, respectively). Autonomic nerve function and subjective feelings, such as fatigue and concentration, were measured before food intake and after the second task to assess the participant's state. The results showed that the average reaction time between the first and second sessions was not significantly different for either high- or low-concentration chocolate consumption. However, the percentage of correct responses was similar in the first (96.7 %) and second (96.8 %) sessions for high-concentration chocolate consumption and significantly lower for low-concentration chocolate consumption in the second (96.4 %) session than in the first session (97.3 %). Autonomic nerve function showed a significant increase in sympathetic nerve activity after the second task with high-concentration chocolate consumption, while subjective feelings showed an increase in mental fatigue for both chocolate types but a significant decrease in concentration only after the second task with low-concentration chocolate consumption. These findings suggest that dark chocolate consumption contributes to the maintenance of performance and concentration in continuous and demanding cognitive tasks

Immunization with a recombinant vaccinia virus that encodes nonstructural proteins of the hepatitis C virus suppresses viral protein levels in mouse liver.

Chronic hepatitis C, which is caused by infection with the hepatitis C virus (HCV), is a global health problem. Using a mouse model of hepatitis C, we examined the therapeutic effects of a recombinant vaccinia virus (rVV) that encodes an HCV protein. We generated immunocompetent mice that each expressed multiple HCV proteins via a Cre/loxP switching system and established several distinct attenuated rVV strains. The HCV core protein was expressed consistently in the liver after polyinosinic acid-polycytidylic acid injection, and these mice showed chronic hepatitis C-related pathological findings (hepatocyte abnormalities, accumulation of glycogen, steatosis), liver fibrosis, and hepatocellular carcinoma. Immunization with one rVV strain (rVV-N25), which encoded nonstructural HCV proteins, suppressed serum inflammatory cytokine levels and alleviated the symptoms of pathological chronic hepatitis C within 7 days after injection. Furthermore, HCV protein levels in liver tissue also decreased in a CD4 and CD8 T-cell-dependent manner. Consistent with these results, we showed that rVV-N25 immunization induced a robust CD8 T-cell immune response that was specific to the HCV nonstructural protein 2. We also demonstrated that the onset of chronic hepatitis in CN2-29((+/-))/MxCre((+/-)) mice was mainly attributable to inflammatory cytokines, (tumor necrosis factor) TNF-α and (interleukin) IL-6. Thus, our generated mice model should be useful for further investigation of the immunological processes associated with persistent expression of HCV proteins because these mice had not developed immune tolerance to the HCV antigen. In addition, we propose that rVV-N25 could be developed as an effective therapeutic vaccine

Improving the Prognosis of Pancreatic Cancer Through Early Detection: Protocol for a Prospective Observational Study

BackgroundPancreatic cancer is associated with high mortality and its rates of detection are very low; as such, the disease is typically diagnosed at an advanced stage. A number of risk factors for pancreatic cancer have been reported and may be used to identify individuals at high risk for the development of this disease. ObjectiveThe aim of this prospective, observational trial is to evaluate a scoring metric for systematic early detection of pancreatic cancer in Mie Prefecture, Japan. MethodsEligible patients aged 20 years and older will be referred from participating clinics in the Tsu City area to the Faculty of Medicine, Gastroenterology, and Hepatology at Mie University Graduate School, until September 30, 2022. Participants will undergo a detailed examination for pancreatic cancer. Data collection will include diagnostic and follow-up imaging data and disease staging information. ResultsThe study was initiated in September 2020 and aims to recruit at least 150 patients in a 2-year period. Recruitment of patients is currently still underway. Final data analysis is expected to be complete by March 2025. ConclusionsThis study will provide insights into the feasibility of using a scoring system for the early detection of pancreatic cancer, thus potentially improving the survival outcomes of diagnosed patients. Trial RegistrationUMIN-CTR Clinical Trials Registry UMIN000041624; https://tinyurl.com/94tbbn3s International Registered Report Identifier (IRRID)DERR1-10.2196/2689