Vaccination with tumor peptide epitopes associated with MHC class I molecules is an attractive approach directed at inducing tumor-specific CTLs. However, challenges remain in improving the therapeutic efficacy of peptide epitope vaccines, including the low immunogenicity of peptide epitopes and insufficient stimulation of innate immune components in vivo. To overcome this, we aimed to develop and test an innovative strategy that elicits potent CTL responses against tumor epitopes. The essential feature of this strategy is vaccination using tumor epitope-loaded nanoparticles (NPs) in combination with polyinosinic-polycytidylic acid (poly-IC) and anti-PD1 mAb. Carboxylated NPs were prepared using poly(lactic-co-glycolic acid) and poly(ethylene/maleic anhydride), covalently conjugated with anti-H-2K b mAbs, and then attached to H-2K b molecules isolated from the tumor mass (H-2 b ). Native peptides associated with the H-2K b molecules of H-2K b -attached NPs were exchanged with tumor peptide epitopes. Tumor peptide epitope-loaded NPs efficiently induced tumor-specific CTLs when used to immunize tumor-bearing mice as well as normal mice. This activity of the NPs significantly was increased when co-administered with poly-IC.Accordingly, the NPs exerted significant anti-tumor effects in mice implanted with EG7-OVA thymoma or B16-F10 melanoma, and the anti-tumor activity of the NPs was significantly increased when applied in combination with poly-IC. The most potent anti-tumor activity was observed when the NPs were co-administered with both poly-IC and anti-PD1 mAb.Immunization with tumor epitope-loaded NPs in combination with poly-IC and anti-PD1 mAb in tumor-bearing mice can be a powerful means to induce tumor-specific CTLs with therapeutic anti-tumor activity.

Abnormal inflammatory responses are closely associated with intestinal microbial dysbiosis. Oral administration of Qmatrix-diabetes-mellitus complex (QDMC), an Aloe gel-based formula, has been reported to improve inflammation in type 2 diabetic mice; however, the role of the gut microbiota in ameliorating efficacy of QDMC remains unclear. We investigated the effect of QDMC on the gut microbiota in a type 2 diabetic aged mouse model that was administered a high-fat diet. Proinflammatory (TNF-α and IL-6) and anti-inflammatory (IL-4 and IL-10) cytokine levels in the fat were normalized via oral administration of QDMC, and relative abundances of Bacteroides, Butyricimonas, Ruminococcus, and Mucispirillum were simultaneously significantly increased. The abundance of these bacteria was correlated to the expression levels of cytokines. Our findings suggest that the immunomodulatory activity of QDMC is partly mediated by the altered gut microbiota composition.

IL-18 is a crucial pro-inflammatory cytokine that mediates chronic intestinal inflammation. Metformin, an anti-diabetic drug, was reported to have ameliorative effects on inflammatory bowel disease. Recently, the mechanism of action of metformin was explained as a modulation of gut microbiota. In this study, fecal microbiota transplantation (FMT) using fecal material from metformin-treated mice was found to upregulate the expression of GLP-1 and pattern-recognition receptors TLR1 and TLR4 for the improvement in hyperglycemia caused by a high-fat diet. Further, FMT downregulated the expression of the inflammatory cytokine IL-18. Within the genera Akkermansia, Bacteroides, and Butyricimonas, which were promoted by metformin therapy, Butyricimonas was found to be consistently abundant following FMT. Our findings suggest that modulation of gut microbiota is a key factor for the anti-inflammatory effects of metformin which is used for the treatment of hyperglycemia.
Animals ; Bacteroides ; Diet, High-Fat ; Down-Regulation ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Glucagon-Like Peptide 1 ; Hyperglycemia ; Inflammation ; Inflammatory Bowel Diseases ; Interleukin-18 ; Metformin ; Mice ; Toll-Like Receptors

Hyperlipidemia, which is closely associated with a fatty diet and aging, is commonly observed in the western and aged society. Therefore, a novel therapeutic approach for this disease is critical, and an immunological view has been suggested as a novel strategy, because hyperlipidemia is closely associated with inflammation and immune dysfunction. In this study, the effects of an aqueous extract of Rubus occidentalis (RO) in obese mice were investigated using immunological indexes. The mice were fed a high-fat diet (HFD) to induce hyperlipidemia, which was confirmed by biochemical analysis and examination of the mouse physiology. Two different doses of RO and rosuvastatin, a cholesterol synthesis inhibitor used as a control, were orally administered. Disturbances in immune cellularity as well as lymphocyte proliferation and cytokine production were significantly normalized by oral administration of RO, which also decreased the elevated serum tumor necrosis factor (TNF)-α level and total cholesterol. The specific immune-related actions of RO comprised considerable improvement in cytotoxic T cell killing functions and regulation of antibody production to within the normal range. The immunological evidence confirms the significant cholesterol-lowering effect of RO, suggesting its potential as a novel therapeutic agent for hyperlipidemia and associated immune decline.
Administration, Oral ; Aging ; Animals ; Antibody Formation ; Cholesterol ; Diet ; Diet, High-Fat ; Homicide ; Hyperlipidemias* ; Inflammation ; Lymphocytes ; Mice ; Mice, Obese* ; Physiology ; Reference Values ; Rosuvastatin Calcium ; Rubus* ; Tumor Necrosis Factor-alpha

OBJECTIVE: To investigate the factors affecting prognosis of extracorporeal shockwave therapy (ESWT) for chronic refractory Achilles tendinopathy (AT). METHODS: Thirty-six patients (48 consecutive feet) with chronic AT (>6 months) and who underwent ESWT for ‘poor’ or ‘fair’ grade in Roles-Maudsley Score (RMS) after unsuccessful conservative treatment were included in the present study. A maximum of 12 sessions of ESWT were conducted until treatment success: RMS reached ‘good’ or ‘excellent’. Termination of ESWT for no response, or ‘poor’ or ‘fair’ grade was regarded as treatment failure. Immediate outcome, long-term outcome (telephone interview after mean 26 months), and factors affecting treatment success were analyzed. RESULTS: Numeric Rating Scale was significantly decreased at immediate and long-term follow-up. Success rate was 71.1% and 90.3%, respectively. Univariate logistic regression identified that immediate treatment success was associated with retrocalcaneal enthesophyte on X-ray (odds ratio [OR], 0.06; 95% confidence interval [CI], 0.01–0.28), pretreatment abnormal ultrasonography echogenicity within Achilles tendon (OR, 18.89; 95% CI, 2.08–171.96), mean duration of ‘post-treatment soreness’ (OR, 0.55; 95% CI, 0.33–0.94), and duration of ‘post-treatment soreness after first ESWT’ (OR, 0.06; 95% CI, 0.01–0.34). The duration of ‘post-treatment soreness after first ESWT’ was found to be the only factor associated with long-term success (OR, 0.32; 95% CI, 0.10–0.99). CONCLUSION: ESWT appears to be effective in achieving long-term success in chronic refractory AT. Immediate success was associated with absence of retrocalcaneal enthesophyte on X-ray, presence of pretreatment abnormal ultrasonography echogenicity, shorter mean duration of ‘post-treatment soreness’, and shorter duration of ‘post-treatment soreness after first ESWT’. The shorter duration of ‘post-treatment soreness after first ESWT’ was identified as the only positive prognostic parameter in achieving long-term success.
Achilles Tendon ; Follow-Up Studies ; High-Energy Shock Waves ; Humans ; Logistic Models ; Prognosis* ; Tendinopathy* ; Treatment Failure ; Treatment Outcome ; Ultrasonography

OBJECTIVE: To develop the Korean version of the Kessler Foundation Neglect Assessment Process (KF-NAP), which enables a more functional assessment of unilateral spatial neglect, by first translating it into Korean and then statistically standardizing it. METHODS: Two rehabilitation specialists translated the KF-NAP into Korean. The entire process of administering the Korean KF-NAP to 30 patients with brain disease was video-recorded. Five occupational therapists from 4 university hospitals nationwide evaluated the 30 video-recorded examination cases. We analyzed inter- and intra-reliabilities of the Korean KF-NAP using the intraclass coefficient and Pearson correlation coefficient. Internal consistency reliability of the assessment categories was also examined using Cronbach's alpha coefficient. RESULTS: For the construct validation study, the Korean KF-NAP was strongly correlated with the Albert's test and letter cancellation test (r ≥ 0.8; p < 0.05). The intraclass correlation coefficients for the first and second assessments of the Korean KF-NAP were 0.973 and 0.982, respectively, showing high reliability (p < 0.05). The intra-rater reliabilities exceeded 0.9 (p < 0.05), and Cronbach's alpha coefficient exceeded 0.8, showing internal consistency reliability. CONCLUSION: The Korean KF-NAP is a reliable and valid instrument for assessing hemispatial neglect symptoms in patients with brain diseases.
Brain Diseases ; Hospitals, University ; Humans ; Perceptual Disorders ; Rehabilitation ; Reproducibility of Results* ; Specialization ; Translating ; Translations

BACKGROUND AND OBJECTIVES: People usually converse in real-life background noise. They experience more difficulty understanding speech in noise than in a quiet environment. The present study investigated how speech recognition in real-life background noise is affected by the type of noise, signal-to-noise ratio (SNR), and age. SUBJECTS AND METHODS: Eighteen young adults and fifteen middle-aged adults with normal hearing participated in the present study. Three types of noise [subway noise, vacuum noise, and multi-talker babble (MTB)] were presented via a loudspeaker at three SNRs of 5 dB, 0 dB, and -5 dB. Speech recognition was analyzed using the word recognition score. RESULTS: 1) Speech recognition in subway noise was the greatest in comparison to vacuum noise and MTB, 2) at the SNR of -5 dB, speech recognition was greater in subway noise than vacuum noise and in vacuum noise than MTB while at the SNRs of 0 and 5 dB, it was greater in subway noise than both vacuum noise and MTB and there was no difference between vacuum noise and MTB, 3) speech recognition decreased as the SNR decreased, and 4) young adults showed better speech recognition performance in all types of noises at all SNRs than middle-aged adults. CONCLUSIONS: Speech recognition in real-life background noise was affected by the type of noise, SNR, and age. The results suggest that the frequency distribution, amplitude fluctuation, informational masking, and cognition may be important underlying factors determining speech recognition performance in noise.
Adult* ; Cognition ; Hearing* ; Humans ; Masks ; Noise* ; Railroads ; Signal-To-Noise Ratio ; Vacuum ; Young Adult