Background
The transcription factor nuclear factor-E2-related factor-2 (Nrf2) inhibits lipid accumulation and oxidative stress in the liver by interfering with lipogenic pathways and inducing ...antioxidative stress genes.
Methods
The involvement of Nrf2 in defense against the development of steatohepatitis was studied in an experimental model induced by an atherogenic plus high-fat (Ath + HF) diet. Wild-type (WT) and
Nrf2
-null mice were fed the diet. Their specimens were analyzed for pathology as well as for the expression levels of genes involved in fatty acid metabolism and those involved via the Nrf2 transcriptional pathway.
Results
In
Nrf2
-null mice fed the diet, steatohepatitis developed rapidly, leading to precirrhosis. The Ath + HF diet increased hepatic triglyceride levels and changed fatty acid composition in both mouse groups. However, oleic acid (C18:1 n-9) predominated in the livers of
Nrf2
-null mice. Correlating well with the pathology, the mRNA levels of the factors involved in fatty acid metabolism (
Lxr
,
Srebp
-
1a
,
1c
,
Acc
-
1
,
Fas
,
Scd
-
1
, and
Fatty acid transporting peptides 1
,
3
,
4
), the inflammatory cytokine genes (
Tnf
-
α
and
IL
-
1β
), and the fibrogenesis-related genes (
Tgf
-
β1
and
α
-
Sma
) were significantly increased in the livers of
Nrf2
-null mice fed the diet, compared with the levels of these factors in matched WT mice. Oxidative stress was significantly increased in the livers of
Nrf2
-null mice fed the diet. This change was closely associated with the decreased levels of antioxidative stress genes.
Conclusions
Nrf2 deletion leads to the rapid onset and progression of steatohepatitis induced by an Ath + HF diet, through both up-regulation of co-regulators of fatty acid metabolism and down-regulation of oxidative metabolism regulators in the liver.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract
The need for support and care is a major problem facing societies around the world. Locomotive syndrome (LS) refers to a condition in which people require healthcare services because of ...problems associated with locomotion. Oral dysfunction is also associated with various long-term care factors including activities of daily living. The purpose of this study was to determine the association between oral dysfunction and LS. The study participants were 407 elderly people living in a rural area in Japan. Evaluation of oral dysfunction was based on subjective judgment by each participant. LS was assessed using Locomo-25, which is a self-administered questionnaire and was defined by a Locomo-25 score ≥ 7 points. Those with a “decline in masticatory function” and “difficulty swallowing” had higher odds of LS than those without these dysfunctions (odds ratio (OR) = 2.134, 2.007, respectively). Furthermore, participants with a Locomo-25 score ≥ 11 had higher odds of a “decline in masticatory function” (OR = 2.657) than those with a Locomo-25 score < 11, and those with a Locomo-25 score ≥ 9 had higher odds of “difficulty swallowing” (OR = 2.411) than those with a Locomo-25 score < 9. These findings suggest that a strong relationship exists between oral dysfunction and LS.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The fruit of Prunus mume (ume, also known as Japanese apricot) has been used as a functional food in Japan since ancient times. We previously reported that ume stimulates the differentiation of ...preosteoblastic cells. Osteocalcin (OCN) is secreted by osteoblasts, and there is known association with glucolipid metabolism and cognitive function. This study sought to clarify the relationship between ume extracts and OCN production both in vitro and in vivo. Alkaline phosphatase activity and OCN level in the ethyl acetate extracts of ume-treated extracts were significantly increased in preosteoblast MC3T3-E1 cells compared with the control group. In human study, serum OCN level was significantly higher in the high ume intake group than in the low intake group in community-dwelling participants over 60 years old. These results suggest that ume has the potential to upregulated OCN production both in vitro and in vivo.
Background
The transcription factor nuclear factor-E2-related factor-2 (Nrf2) is a key regulator for induction of hepatic antioxidative stress systems. We aimed to investigate whether activation of ...Nrf2 protects against steatohepatitis.
Method
Wild-type mice (WT),
Nrf2
gene-null mice (
Nrf2
-null) and
Keap1
gene-knockdown mice (
Keap1
-kd), which represent the sustained activation of Nrf2, were fed a methionine- and choline-deficient diet (MCDD) for 13 weeks and analyzed.
Results
In
Keap1
-kd fed an MCDD, steatohepatitis did not develop over the observation periods; however, in
Nrf2
-null fed an MCDD, the pathological state of the steatohepatitis was aggravated in terms of fatty change, inflammation, fibrosis and iron accumulation. In WT mice fed an MCDD, Nrf2 and antioxidative stress genes regulated by Nrf2 were potently activated in the livers, and in
Keap1
-kd, their basal levels were potently activated. Oxidative stress was significantly increased in the livers of the
Nrf2
-null and suppressed in the livers of the
Keap1
-kd compared to that of WT, based on the levels of 4-hydroxy-2-nonenal and malondialdehyde. Iron accumulation was greater in the livers of the
Nrf2
-null mice compared to those of the WT mice, and it was not observed in
Keap1
-kd. Further, the iron release from the isolated hepatocyte of
Nrf2
-null mice was significantly decreased. Sulforaphane, an activator of Nrf2, suppressed the pathological states and oxidative stress in the livers.
Conclusions
Nrf2 has protective roles against nutritional steatohepatitis through inhibition of hepatic iron accumulation and counteraction against oxidative stress-induced liver injury. Nrf2 activation by pharmaceutical intervention could be a new option for the prevention and treatment of steatohepatitis.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Our study investigated the relationship between gastric cancer development and activity of Helicobacter pylori‐associated chronic gastritis or the resulting chronic atrophic gastritis (CAG). A cohort ...of 4,655 healthy asymptomatic subjects, in whom serum pepsinogen (PG) and H. pylori antibody titer had been measured to assess the activity and stage of H. pylori‐associated chronic gastritis, was followed for up to 16 years, and cancer development was investigated. In subjects with a serologically diagnosed healthy stomach (H. pylori‐negative/CAG‐negative), cancer incidence rate was low, at 16/100,000 person‐years. With the establishment of H. pylori infection and progression of chronic gastritis, significant stepwise cancer risk elevations were seen from CAG‐free subjects (H. pylori‐positive/CAG‐negative) hazard ratio (HR) = 8.9, 95% confidence interval (CI) = 2.7–54.7 to subjects with CAG (H. pylori‐positive/CAG‐positive) (HR = 17.7, 95% CI = 5.4–108.6) and finally to subjects with metaplastic gastritis (H. pylori‐negative/CAG‐positive) (HR = 69.7, 95% CI = 13.6–502.9). In H. pylori‐infected CAG‐free subjects, significantly elevated cancer risk was observed in the subgroup with active inflammation‐based high PG II level or potent immune response‐based high H. pylori antibody titer; the former was associated with a particularly high risk of diffuse‐type cancer, and both subgroups showed high cancer incidence rates of around 250/100,000 person‐years, comparable to that in subjects with CAG. No such risk elevation was observed in H. pylori‐infected subjects with CAG. These results clearly indicate that gastric cancer develops mainly from the gastritis‐atrophy‐metaplasia‐cancer sequence and partly from active inflammation‐based direct carcinogenesis, and that serum levels of PG and H. pylori antibody titer provide indices of cancer development in H. pylori‐infected subjects.
What's new?
Infection with the bacteria H. pylori is the most common risk factor for developing gastric cancer. The infection causes chronic inflammation leading to a sequence of gastritis, atrophy, metaplasia, dysplasia, cancer. This study follows up a cohort of 6,000 men after 16 years and showed that cancer risk increased with the progression of inflammation and atrophy, which can be measured by serum tests. These tests, the authors suggest, would be useful in assessing risk among people infected with H. pylori.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Abstract
Osteoporosis is a complication of diabetes mellitus (DM). The pathology of diabetic osteoporosis is distinct from postmenopausal osteoporosis, and there are no specific treatment guidelines ...for diabetic osteoporosis. In the current study, this issue was addressed by evaluating the effect of osteoporosis medications, such as the anabolic agent PTH teriparatide (TPTD) and the antiresorptive agents calcitonin elcatonin (ECT) and bisphosphonate risedronate (RIS), on bone metabolism as well as on glucose and lipid metabolism in spontaneously diabetic Torii (SDT) fatty rats, which are a model of type 2 DM (T2DM). The medicines were injected subcutaneously into 8-week-old male SDT fatty rats three times weekly for 8 weeks. TPTD treatment in SDT fatty rats increased the osteoblast number and function on trabecular bone in vertebrae, and increased the trabecular bone mass, bone mineral density (BMD), and mechanical strength of vertebrae. Additionally, TPTD improved cortical bone structure and increased BMD. RIS decreased the osteoclast number and function, which led to an increase in vertebral bone mineral content and BMD in the femoral diaphysis, and mechanical strength was increased in the vertebrae. ECT showed no clear effects on bone mass or metabolism. Similar to diabetic lesions, all of the drugs had no effects on hyperglycemia, pancreas morphology, or serum insulin and glucagon levels. However, triglyceride levels and lipid droplets in fatty liver were decreased in the TPTD group. These results suggest that TPTD may be useful for treating fatty liver in addition to osteoporosis in T2DM.
Caffeic acid has been shown to inhibit the multiplication of influenza A virus in vitro, whereas caffeine, quinic acid and chlorogenic acid do not. Caffeic acid has also been shown to have antiviral ...activity against herpes simplex virus (DNA virus) and polio virus (RNA virus). In the present study, a comparison of the one-step growth curve of the influenza virus in the presence of caffeic acid with that in the absence of the reagent showed that an eclipse period of the virus multiplication in the infected cells was not affected by the reagent, while the progeny virus yield was markedly decreased in the presence of caffeic acid. In additional experiments, it was found that the addition of caffeic acid at an early time point post-infection (within 3 h post-infection) was mandatory for extensive antiviral activity, suggesting that a major target of the reagent exists in the early stages of infection. Simultaneously with the decrease in the progeny virus yield, both the virus-induced cytopathic effects and apoptotic nuclear fragmentation were markedly suppressed by the reagent, suggesting that caffeic acid suppresses, at least temporally, the degeneration of the virus-infected cells and that the observed antiviral activity is likely not the secondary result of the cytotoxic effects of the reagent. These results suggest the potential pharmacological use of caffeic acid or its derivatives as an antiviral drug against influenza A virus.
Japanese apricot (Prunus mume; ume) is a traditional food in Japan that has been shown to have various beneficial health effects. There is some evidence to suggest that ume is also effective against ...allergic disease. Here, we conducted a cross-sectional epidemiological pilot study to examine the association between ume intake frequency and allergic symptoms including rhinitis in 563 adults (288 men and 275 women) who resided in Wakayama, Japan. After adjusting for age, present illness and medication, women with high ume intake had significantly lower odds ratio (OR) for the presence of symptoms of allergy OR: 0.49 with 95% confidence interval (CI): 0.25-0.97. Therefore, we investigated the anti-allergic effect of ume on passive cutaneous anaphylaxis (PCA) reaction in immunoglobulin E (IgE)-sensitized mice. The animal study demonstrated that oral administration of ume extract attenuated the PCA reaction and mast cell degranulation. Furthermore, RBL-2H3 mast cells were used to identify anti-allergic ume compounds. The following ume compounds inhibited IgE-mediated mast cell degranulation: vanillin, syringic acid, protocatechuic aldehyde, lyoniresinol and p-coumaric acid. These results suggested that ume has the potential to inhibit mast cell degranulation and may be associated with reduced risk of allergic symptoms in women.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Locomotive syndrome (LS) is a concept that refers to the condition of people requiring healthcare services because of problems associated with locomotion. Depression is a major psychiatric disease ...among the elderly, in addition to dementia. The purpose of this study was to determine the association between LS and depression. The study participants were 224 healthy elderly volunteers living in a rural area in Japan. LS was defined as scores ≥ 16 on the 25-question Geriatric Locomotive Function Scale (GLFS-25). Depression was defined as scores ≥ 5 on the 15-item Geriatric Depression Scale (GDS-15). Height and body weight were measured. The prevalence of LS and depression was 13.9% and 24.2%, respectively. Compared with the non-LS group, the LS group was older, was shorter, had a higher BMI, and had higher GDS-15 scores. Logistic regression analysis showed that participants with GDS-15 scores ≥ 6 had higher odds for LS than those with GDS-15 scores < 6 (odds ratio OR = 4.22). Conversely, the depression group had higher GLFS-25 scores than the nondepression group. Participants with GLFS-25 scores ≥ 5 had higher odds for depression than those with GLFS-25 scores < 5 (OR = 4.53). These findings suggest that there is a close relationship between LS and depression.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK