Iron supplementation regulates the progression of high fat diet induced obesity and hepatic steatosis via mitochondrial signaling pathways.

Disruption of iron metabolism is closely related to metabolic diseases. Iron deficiency is frequently associated with obesity and hepatic steatosis. However, the effects of iron supplementation on obesity and energy metabolism remain unclear. Here we show that a high-fat diet supplemented with iron reduces body weight gain and hepatic lipid accumulation in mice. Iron supplementation was found to reduce mitochondrial morphological abnormalities and upregulate gene transcription involved in mitochondrial function and beta oxidation in the liver and skeletal muscle. In both these tissues, iron supplementation increased the expression of genes involved in heme or iron-sulfur (Fe-S) cluster synthesis. Heme and Fe-S cluster, which are iron prosthetic groups contained in electron transport chain complex subunits, are essential for mitochondrial respiration. The findings of this study demonstrated that iron regulates mitochondrial signaling pathways-gene transcription of mitochondrial component molecules synthesis and their energy metabolism. Overall, the study elucidates the molecular basis underlying the relationship between iron supplementation and obesity and hepatic steatosis progression, and the role of iron as a signaling molecule.

Asperuloside Improves Obesity and Type 2 Diabetes through Modulation of Gut Microbiota and Metabolic Signaling.

Asperuloside (ASP) is an iridoid glycoside that is extracted from Eucommia leaves. Eucommia is used in traditional Chinese medicine and has a long history of benefits on health and longevity. Here, we investigated the impact of ASP on obesity-related metabolic disorders and show that ASP reduces body weight gain, glucose intolerance, and insulin resistance effectively in mice fed with a high-fat diet (HFD). Intestinal dysbiosis is closely linked with metabolic disorders. Our data indicate that ASP achieves these benefits on metabolic homeostasis by reversing HFD-induced gut dysbiosis and by changing gut-derived secondary metabolites and metabolic signaling. Our results indicate that ASP may be used to regulate gut microbiota for the treatment of obesity and type 2 diabetes.

Melon GliSODin® Prevents Diet-Induced NASH Onset by Reducing Fat Synthesis and Improving Liver Function.

A high-calorie diet causes fat accumulation and oxidative stress in the liver, leading to fatty liver and eventually non-alcoholic steatohepatitis (NASH). Melon GliSODin® is used as a nutritional supplement because of its antioxidant activity. This study aimed to assess the antioxidant activity of Melon GliSODin® and its effectiveness in preventing NASH, which primarily results from oxidative stress. Furthermore, we verified the protective effect of Melon GliSODin® by administering it to a mouse model of diet-induced NASH. Melon GliSODin® suppressed liver fibrosis and fat accumulation, which is characteristic of the NASH phenotype. Gene expression analysis confirmed the suppression of fat synthesis and activation of antioxidative mechanisms. These results show that Melon GliSODin® mitigates NASH onset at the molecular level, suggesting its potential application as a NASH preventive agent.

Topical betamethasone butyrate propionate exacerbates pressure ulcers after cutaneous ischemia-reperfusion injury.

Ischaemia-reperfusion (I/R) is involved in the development of various organ diseases. There has been increasing evidence that cutaneous I/R injury is associated with the pathogenesis of pressure ulcers (PUs), especially at the early stage presenting as non-blanchable erythema. However, there is no evidence-based treatment for early-stage PUs. Our objective was to assess the effects of topical steroid on the development of PUs after cutaneous I/R injury in mice. Cutaneous I/R was performed by trapping the dorsal skin between two magnetic plates for 12 h, followed by plate removal. Topical application of betamethasone butyrate propionate (BBP) in I/R areas significantly increased the size of PUs after I/R. The number of thromboses was increased, and CD31(+) vessels were decreased in the I/R area treated with topical BBP. The number of oxidative stress-associated DNA-damaged cells and apoptotic cells in the I/R area was increased by topical BBP treatment. In addition, the mRNA level of NADPH oxidase 4 (Nox4), the essential enzyme that produces reactive oxygen species, was significantly increased and that of NF-E2-related factor 2 (Nrf2), a transcription factor that regulates the expression of antioxidant proteins, was inhibited in the I/R area treated by BBP. The number of CD68(+) macrophages and the level of transforming growth factor-beta in lesional skin were also decreased by BBP. These results suggest that a topical steroid might accelerate the formation of PUs induced by cutaneous I/R injury by aggravating oxidative stress-induced tissue damage. Topical steroids might not be recommended for the treatment of acute-phase decubitus ulcers.

Placebo controlled evaluation of Xilei San, a herbal preparation in patients with intractable ulcerative proctitis.

BACKGROUND AND AIM: Topical mesalamine or corticosteroid has shown efficacy in patients with ulcerative proctitis, but patients often become refractory to these interventions. Xilei San is a herbal preparation with evidence of anti-inflammatory effects. We evaluated the efficacy of topical Xilei San in ulcerative proctitis patients. METHODS: In a double blind setting, 30 patients with intractable ulcerative proctitis despite ≥ 4 weeks of topical mesalamine or corticosteroid were randomly assigned to True (n = 15) and placebo (n = 15). Patients in True received suppository Xilei San (0.1 g/dose per day of Xilei San), the other 15 received placebo suppository. The initial efficacy was evaluated on day 14. Primary endpoint of the trial was avoiding relapse during 180 days, relapse meant recurrence of active disease. Riley's index was applied for endoscopic and histological evaluations, while patients' quality of life was evaluated by an inflammatory bowel disease questionnaire. RESULTS: On day 14, the number of patients who achieved remission, clinical activity index ≤ 4 in True was significantly higher versus placebo (P < 0.04). Likewise, at day 180, an 81.8% of patients in True were without relapse versus 16.7% in placebo (P < 0.001). Further, significant endoscopic (P < 0.01), histological (P < 0.02) and inflammatory bowel disease questionnaire (P < 0.04) improvements were observed in True, but not in placebo. CONCLUSIONS: This is the first controlled investigation showing significant clinical and endoscopic efficacy for Xilei San in patients with intractable ulcerative proctitis. Topical Xilei San was well tolerated, and was without safety concerns.

Research into acupuncture for respiratory disease in Japan: a systematic review.

BACKGROUND: In Japan, studies on acupuncture therapy for respiratory disease have rarely been reported. Additionally, most of the reports are difficult for overseas researchers to access because they are written in Japanese and cannot be located using Medline. PURPOSE: To review studies on acupuncture and moxibustion therapy for respiratory disease conducted in Japan. DATA SOURCES: The results of a literature search using "Igaku Chuo Zasshi Web" and the Medical Online Library, both of which are Japanese databases, covering the period between 1979 and 2006. STUDY SELECTION: This study reviewed references cited in retrieved documents and selected original articles and case reports on acupuncture and moxibustion therapy for respiratory disease. DATA EXTRACTION: The search terms used were "acupuncture" and "respiratory disease", along with "respiratory", "asthma", "COPD", "bronchitis" and "common cold". RESULTS: The study retrieved 34 papers on acupuncture treatment for respiratory disease written in Japanese (9 full papers, 19 case reports and 6 case series). The papers dealt with such conditions as asthma (14 trials), cough variant asthma (one trial), chronic obstructive pulmonary disease (seven trials), chronic bronchitis (one trial), usual/idiopathic interstitial pneumonia (one trial) and the common cold (two trials). The study also found eight trials dealing with cold prevention. CONCLUSIONS: A small number of reports on acupuncture and moxibustion treatment for respiratory diseases were found in the Japanese databases. Future studies must use more rigorous evaluation methods, such as randomised controlled trials, to measure the effectiveness of acupuncture and moxibustion therapy for treating respiratory diseases.

Clinical usefulness of a supplementary cyclosporin administration with a topical application of maxacalcitol ointment for patients with moderate psoriasis vulgaris.

In this study, we aimed at confirming the clinical usefulness of a supplementary additional cyclosporin microemulsion preconcentrate (CyA MEPC) administration in 15 patients with psoriasis vulgaris whose disease activity had been unchanged or exacerbated with topical maxacalcitol treatment. Each patient took a supplementary CyA MEPC administration, 2.5 mg/kg per day in addition to maxacalcitol ointment therapy. When the Psoriasis Area and Severity Index (PASI) score revealed over a 75% decrease against the initial value, the administration of CyA MEPC was tapered off, and a topical application of maxacalcitol ointment was continued for the maintenance phase. All patients could obtain improvement within 12 weeks. In 12 patients whose PASI score reduced over 75%, CyA MEPC was tapered off. Of those, five patients remained in remission by maxacalcitol ointment for over 12 months and three patients for 6 months. In conclusion, this preliminary study may suggest that supplementary therapy of short-term CyA MEPC administration in combination with topical vitamin D3 treatment may be worth trying for patients with moderate psoriasis vulgaris.

The effect of acupuncture in the treatment of chronic obstructive pulmonary disease.

OBJECTIVE: Many claims have been made regarding the therapeutic efficacy of acupuncture. However, most controlled clinical studies have been limited to treatment of pain-related disorders and do not provide objective, quantifiable data for analysis. Traditional acupuncture has been applied to chronic obstructive pulmonary disease (COPD). However, only a few studies have been performed to determine the efficacy of this treatment. This study was conducted to determine whether a combination of traditional acupuncture treatment and conservative treatment for COPD improves dyspnea on exercise. METHODS: This was a prospective trial with matched-pair parallel groups of patients from the departments of respiratory internal medicine of Gifu University of Medicine, Meiji University of Oriental Medicine, and Gifu Red Cross Hospital, Japan. Thirty patients were divided into the acupuncture group (n = 15) and the control group (n = 15). The control group received conservative treatment with medication only. The acupuncture group received acupuncture treatments once a week for 10 weeks, in addition to conservative treatment with medication. The main outcome measure was the Modified Borg dyspnea scale after the 6-minute walk test. RESULTS: The acupuncture group had significantly better results on the Borg scale than the control group after 10 weeks (2.2 +/- 2.7 versus 6.4 +/- 3.4, p = 0.0001, 95% confidence interval, -5.10 to -2.35, paired t-test). The 6-minute walk distance and oxygen saturation at the minimum rate improved significantly in the acupuncture group compared with the control group. CONCLUSIONS: This study demonstrated that acupuncture contributed to the reduction of COPD-related dyspnea on exercise in 15 matched-pair parallel subjects.

Effect of activated human mast cells and mast cell-derived mediators on proliferation, type I collagen production and glycosaminoglycans synthesis by human dermal fibroblasts.

Although an increased number of mast cells in fibrotic tissues such as scleroderma, keloid or healing wound has been highlighted, it is still unclear whether or not mast cells are fibrogenic. The aim of the present study is to determine whether functionally active human mast cells can provide human dermal fibroblasts directly with fibrogenic properties. In order to examine the effects of IgE-mediated mast cell activation on fibroblast proliferation and synthesis of type I collagen, we utilized an in vitro defined system in which cultured human mast cells were co-cultured with human dermal fibroblasts. We also employed a three-dimensional fibroblast culture system using supplementation of L-ascorbic acid as an assay system to investigate the effects of mast cell-derived mediators on synthesis of glycosaminoglycans by human fibroblast. Fibroblast proliferation was actively stimulated with IgE-activated mast cells. However, this stimulatory effect was canceled in co-cultures with a higher number of IgE-activated mast cells. In the presence of a higher number of activated mast cells, the fibroblast cell layer was destroyed, in contrast to an intact cell layer in the presence of same number of the mast cells without activation. Type I collagen synthesis was unchanged in fibroblasts co-cultured with mast cells. The total amount of main disaccharide units, particularly DELTADi-HA, was increased when fibroblasts were exposed to histamine. Thus, we conclude that other factors, in addition to mast cells, are important in the development of human tissue fibrosis or sclerosis.