Dysfunction of the Murine Liver with Aging and Its Improvement with the Continuous Consumption of Enterococcus faecalis EC-12.

Chronic inflammation is involved in the development of age-related diseases. Given its persistence, controlling chronic inflammation is essential for preventing age-related diseases. In this study, we investigated the effects of Enterococcus faecalis EC-12 (EC-12), which has immunomodulatory and antioxidant effects, on liver gene expression and aging phenomena in mice. Short-term EC-12 administration stimulated the expression of genes involved in lipid synthesis and metabolism in the liver. Furthermore, long-term EC-12 administration from 10 weeks to 1.5 years of age resulted in significant increases in blood interleukin (IL)-6 and IL-10 concentrations (both p < 0.05) and a significant decrease in the monocyte chemotactic protein-1 concentration (p < 0.05). These results indicated pathologic improvement, such as suppression of fat degeneration in the liver. These results suggest that continuous EC-12 intake from a young age can suppress liver function abnormalities, which is one of the aging phenomena in old age, and contribute to health in old age.

Oral supplementation of a cell preparation of Enterococcus faecalis strain EC-12 stimulates superoxide dismutase production in the livers of healthy and arthritis-induced mice.

Hepatitis, a major human chronic inflammation disease, has been linked to oxidative stress, which can be initiated by radicals produced during the oxidative metabolism. Oxidative damage has been also observed in arthritis-induced mice. Here we evaluated whether supplementation of a cell preparation of Enterococcus faecalis EC-12 could induce superoxide dismutase activity and/or damage in the livers of healthy mice or mice with arthritis. In Experiment 1, both healthy and arthritis-induced mice were orally given a saline solution, or a solution with a low (0.2 mg/mouse/day) or a high (2.0 mg/mouse/day) concentration of E. faecalis EC-12 for 49 consecutive days. Manganese superoxide dismutase activity increased in E. faecalis EC-12-supplemented mice but with no arthritis. In Experiment 2, mice received orally either a saline or an E. faecalis EC-12 suspension (10 mg/kg of body weight/day) for 28 consecutive days. No changes in tissues and levels of function markers and 8-hydroxy-2'-deoxyguanosine were observed in mouse livers, inferring that E. faecalis EC-12 supplementation caused no damage. While mRNA expression of copper/zinc superoxide dismutase remained unaltered, that of manganese superoxide dismutase increased in E. faecalis EC-12 administration mice. In conclusion, at least in healthy mice, E. faecalis EC-12 supplementation stimulated manganese superoxide dismutase activity in liver tissues with no side effects.

Edible bird's nest extract downregulates epidermal apoptosis and helps reduce damage by ultraviolet radiation in skin of hairless mice.

The purpose of the present study was to examine whether daily intake of edible bird's nest extract reduced ultraviolet-induced damage to skin. Twenty-one female HR-1/Hos mice were divided into control (C, n = 7), low-dose (2 mg/kg body weight/day of edible bird's nest extract) (L, n = 7), and high-dose (20 mg/kg body weight/day of edible bird's nest extract) (H, n = 7) groups. With their left back skin covered with aluminum sheet to prevent exposure, mice were radiated with either ultraviolet A (20 J/cm2) or ultraviolet B (40 mJ/cm2) in an alternate manner once daily for 10 weeks. They were gavaged either a solution of saline or edible bird's nest extract every day. The moisture content of the ultraviolet-exposed right back skin was significantly higher in H than in C or L. Histochemical analysis showed that the number of apoptotic epidermal cells on the ultraviolet-exposed skin was significantly lower in L and H than in C. In H, the mRNA expression of superoxide dismutase 2 was significantly higher on ultraviolet-exposed skin than on unexposed skin. Our data suggested that edible bird's nest extract enhanced superoxide dismutase 2 expression and downregulated apoptosis in their epidermis, which likely helped reduce skin damage.

Heat-killed Enterococcus fecalis (EC-12) supplement alters the expression of neurotransmitter receptor genes in the prefrontal cortex and alleviates anxiety-like behavior in mice.

Gut microbiota plays a crucial role in the maintenance of mental health and influences mental disorders such as depression and anxiety. Several studies have reported the beneficial affects of probiotics in mental health. Heat-killed Enterococcus faecalis strain EC-12 (EC-12), a lactic acid bacterium induces activation of the immune system. However, little is known about the effect of EC-12 on mental health. In the present study, the anti-anxiety effect of EC-12 was elucidated in vivo. Male mice fed on diet supplemented with EC-12 showed decreased anxiety-like behavior in open-field and elevated plus-mazetest. In addition, EC-12 supplementation exhibited an anti-depressive trend in mice subjected to forced swim test. The expression of neurotransmitter receptor genes: Adrb3 and Avpr1a were significantly enhanced in EC-12 supplemented mice compared to that of the control mice. In mice, analyses of gut microbiota composition by next generation sequencing revealed significant increase in Butyricicoccus and Enterococcus with EC-12 supplementation. Significant difference was not detected in the expression of neurotransmitter receptor genes in the prefrontal cortex with the administration of sodium butyrate compared to that of the control group. The mechanism associated with EC-12 mediated reduced anxiety-like behavior and altered gene expression in the brain needs to be further elucidated. Taken together, the present study is the first to report the possibility of exploiting the anti-anxiety effect of heat-killed EC-12 as a novel probiotic to promote mental health.

Exploratory investigation of the anti-inflammatory effects of RNase A-treated Enterococcus faecalis strain EC-12.

We previously reported that the major component of Enterococcus faecalis strain EC-12 (EC-12) inducing production of Interleukin (IL)-12 in mouse/human immune cells was its own RNA. This study aimed to investigate if RNase A-treated EC-12 could also produce IL-10 and to evaluate the possible effects of IL-10 produced by RNase A-treated EC-12. Three experiments were conducted: (1) Assessment of the effect of RNase A-treated EC-12 on transcriptome profiles and biological pathways in human peripheral blood mononuclear cells; (2) Determination of cytokine concentration in its culture supernatants; and (3) Supplementation of RNase A-treated EC-12 (RN) to mice with dextran sodium sulfate-induced colitis. Treatment of EC-12 with RNase A inhibited inflammatory response including the potency to induce IL-12 production, while it did not affect IL-10 production (Experiment 1 and 2). Colitis symptoms were milder in RN than in PBS-supplemented controls (Experiment 3). RNase A-treated EC-12 likely became an anti-inflammatory agent primarily inducing IL-10 production.

Fragmented CagA protein is highly immunoreactive in Japanese patients.

BACKGROUND: High-molecular-weight cell-associated proteins (HM-CAP) assay is the most popular serological immunoassay worldwide and has been developed from US isolates as the antigens. The accuracy is reduced when the sera are from adults and children in East Asia including Japan. To overcome the reduced accuracy, an enzyme immunoassay using Japanese strain-derived HM-CAP (JHM-CAP) was developed, in which the antigens were prepared by exactly the same procedure as HM-CAP. The performance of JHM-CAP was better than that of HM-CAP in Japanese adults as well as in children. The higher sensitivity was because of the presence of 100-kDa protein that was absent in the preparation of HM-CAP antigen. MATERIALS AND METHODS: Immunoblot analysis and peptide mass fingerprinting methods were used to identify the distinctive 100-kDa protein present in JHM-CAP antigens. The peptide sequence and identification were analyzed by Mascot Search on the database of Helicobacter pylori. The identified protein was confirmed by immunoblot with a specific antibody and inhibition assay by the sera. RESULTS: The distinctive 100-kDa protein was a fragment of CagA derived from Japanese clinical isolates, and the sera of Japanese patients had strongly reacted to the protein, probably to the exposed epitope on the fragmented CagA. The fragmentation of CagA had occurred in the process of antigen preparation in Japanese isolates, not in US isolates even under the same preparation. CONCLUSION: The distinctive 100-kDa protein was a fragment of CagA protein of H. pylori derived from Japanese clinical isolates, and Japanese patients including children are likely to react strongly to the exposed epitopes on fragmented CagA.

Efficacy of weekly paclitaxel in patients with advanced gastric cancer refractory to docetaxel-based chemotherapy.

BACKGROUND: Only partial cross-resistance between docetaxel and paclitaxel has been demonstrated in breast and ovarian cancers. Whether weekly paclitaxel is effective in patients with advanced gastric cancer refractory to docetaxel-based chemotherapy remains unclear, and we aimed to clarify the efficacy and safety of weekly paclitaxel in such patients. METHODS: Patients who had received docetaxel-based regimens were assigned to the prior-docetaxel group, and those who had never received docetaxel were designated as the non-docetaxel group. Paclitaxel at 80 mg/m(2) was administered by intravenous infusion in all patients, and this was repeated weekly for 3 weeks out of 4. RESULTS: Between April 2006 and June 2011, 65 patients were studied: 26 in the prior-docetaxel group and 39 patients were non-docetaxel group. The median age, gender, performance status, histological type, history of gastrectomy, and the locations and numbers of metastatic sites did not differ significantly between the two groups. In the prior-docetaxel group, the response rate (RR) was 14.2% (3/21) among patients with measurable lesions, median progression-free survival (PFS) was 79 days [95% confidence interval (CI), 47-135 days], and overall survival (OS) was 123 days (95% CI, 90-215 days) from the initiation of paclitaxel treatment. In the non-docetaxel group, the RR was 11.5% (3/26) among patients with measurable lesions, PFS was 82 days (95% CI, 52-106 days), and OS was 143 days (95% CI, 121-178 days). The efficacy of weekly paclitaxel thus appeared to be similar in the two groups. CONCLUSIONS: Weekly paclitaxel was modestly active in patients with gastric cancer refractory to docetaxel-based chemotherapy.

[Infliximab-induced lupus erythematosus in a case of ulcerative colitis].

Infliximab is widely used in the treatment of inflammatory bowel disease, but despite its good clinical efficacy and tolerance, drug-induced autoimmune disorders have been reported as adverse reactions and are a matter of concern. Here we report a patient with ulcerative colitis who developed drug-induced lupus erythematosus after infliximab treatment. While this is a rare complication of infliximab, early diagnosis and successful management are essential.

Esophageal small-cell carcinoma with syndrome of inappropriate secretion of antidiuretic hormone.

Small-cell carcinoma (SCC) of the esophagus is rare, and its clinical characteristics remain poorly understood. A 54-year-old man was given a diagnosis of esophageal SCC and underwent esophagectomy. Four months after surgery, he was admitted to our hospital because of rapidly developing hyponatremia. Syndrome of Inappropriate Secretion of Antidiuretic Hormone (SIADH) due to extensive recurrence of SCC was diagnosed. Combined chemotherapy with irinotecan and cisplatin has dramatically reduced metastatic tumors, and it was concomitantly effective for SIADH. This case demonstrates that esophageal SCC could induce SIADH as a paraneoplastic syndrome and that the above combined chemotherapy was feasible and effective.

[A case of pancreatic acinar cell carcinoma with a giant liver metastasis successfully treated with combination of gemcitabine and peroral S-1].

Pancreatic acinar cell carcinoma is rare, and its incidence is less than 1% of all the malignant pancreatic tumors. Little is reported on effectiveness of chemotherapy. We report a 64-year-old male patient with pancreatic acinar cell carcinoma and a giant metastatic liver tumor, which responded to combination chemotherapy with gemcitabine(GEM)and peroral S-1 administration. The patient had upper abdominal pain and hypervascular tumors in liver(15 cm in diameter)and pancreas tail (3 cm in diameter), which were detected by an enhanced abdominal computed tomography(CT)scan, and was admitted for further examination. Abdominal angiography, FDG-positron emission tomography(PET), and liver tumor biopsy led to a diagnosis of pancreatic acinar cell carcinoma in the pancreas tail with liver metastasis. The patient was then treated with combination chemotherapy, which consisted of intravenous infusion of GEM and peroral administration of S-1, and the metastatic liver tumor was markedly reduced(partial response in RECIST). Although the prognosis of patients with unresectable pancreatic acinar cell cancers is generally unfavorable, it is suggested that the GEM/S- 1 combination chemotherapy is effective for these patients' treatment.