Dietary characteristics associated with the risk of non-alcoholic fatty liver disease and metabolic dysfunction-associated steatotic liver disease in non-obese Japanese participants: A cross-sectional study.

Background and Aim: Dietary characteristics associated with non-alcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated steatotic liver disease (MASLD) in non-obese patients remain to be elucidated. This study examined the association of NAFLD and MASLD with dietary characteristics according to obesity status. Methods: We performed a cross-sectional study of 15 135 participants (n = 7568 men and 7567 women) aged 35-74 years using data of annual health checks between 2008 and 2020. Obesity was defined as BMI ≥ 25 kg/m2. Diagnosis of fatty liver was based on abdominal ultrasonography. Fatty-liver-related dietary characteristics were assessed using a self-administered questionnaire. Results: For non-obese participants, NAFLD was found in 31.0% of men and 19.4% of women. Non-obese MASLD was found in 27.6% of men and 18.1% of women. Multivariable-adjusted stepwise logistic regression analysis indicated that, in males, both non-obese NAFLD and non-obese MASLD were significantly and negatively associated with "often eat sesame/nuts", and positively associated with "often eat noodles/rice bowl" and "often eat evening meal" (P < 0.05). For non-obese women, both NAFLD and MASLD were significantly and positively associated with "often eat sweet buns/bread with fillings" (P < 0.05). Adjusted analyses showed that all dietary characteristics were not significantly associated with the risk of NAFLD/MASLD in obese men and women. Conclusion: This cross-sectional study indicates the existence of sex and obesity differences in the association of NAFLD and MASLD with dietary characteristics. Our findings suggest that some dietary characteristics are associated with NAFLD and MASLD prevalence in non-obese Japanese participants.

Favorable Dietary Patterns Associated with Lower Incidence of Metabolic Syndrome in Middle-Aged Japanese Men: A Prospective Cohort Study.

Dietary patterns, such as selecting what food to regularly eat, may play role in reducing the incidence of metabolic syndrome (MetS). This study examined the causal relationships of Japanese dietary patterns and the relationship with the risk of MetS onset using a prospective cohort design. Data of annual health checks between 2008 and 2017 were analyzed, and middle-aged men and women (n=3,298 and 3,925, respectively) were followed up for 15,498 and 19,459 person-years, respectively. We investigated six dietary patterns using a questionnaire, and the participants were divided into low, middle, and high dietary score groups. During the follow-up period, cases of new-onset MetS were found in 698 men (21.2%) and 350 women (8.2%). Covariate-adjusted Cox proportional hazard models revealed that the risk of new-onset MetS was significantly lower in the male participants who responded that they "often eat vegetables" (HR: 0.77, 95% CI: 0.66-0.91). For dietary score, the male participants had significantly lower adjusted HRs of MetS onset in the middle-score group (HR: 0.80, 95% CI: 0.69-0.94) and high-score group (HR: 0.54, 95% CI: 0.41-0.72) compared to the low-score group. On the other hand, there was no association of each dietary pattern and dietary score with new-onset MetS among the female participants. This study found that favorable dietary patterns are associated with a lower risk of MetS; thus, education that aims to encourage a favorable diet may have an important role in reducing the incidence of MetS in middle-aged men.

Tri-membrane nanoparticles produced by combining liposome fusion and a novel patchwork of bicelles to overcome endosomal and nuclear membrane barriers to cargo delivery.

Membrane fusion is a rational strategy for crossing intracellular membranes that present barriers to liposomal nanocarrier-mediated delivery of plasmid DNA into the nucleus of non-dividing cells, such as dendritic cells. Based on this strategy, we previously developed nanocarriers consisting of a nucleic acid core particle coated with four lipid membranes [Akita, et al., Biomaterials, 2009, 30, 2940-2949]. However, including the endosomal membrane and two nuclear membranes, cells possess three intracellular membranous barriers. Thus, after entering the nucleus, nanoparticles coated with four membranes would still have one lipid membrane remaining, and could impede cargo delivery. Until now, coating a core particle with an odd number of lipid membranes was challenging. To produce nanocarriers with an odd number of lipid membranes, we developed a novel coating method involving lipid nano-discs, also known as bicelles, as a material for packaging DNA in a carrier with an odd number of lipid membranes. In this procedure, bicelles fuse to form an outer coating that resembles a patchwork quilt, which allows the preparation of nanoparticles coated with only three lipid membranes. Moreover, the transfection activity of dendritic cells with these three-membrane nanoparticles was higher than that for nanoparticles coated with four lipid membranes. In summary, we developed novel nanoparticles coated with an odd number of lipid membranes using the novel "patchwork-packaging method" to deliver plasmid DNA into the nucleus via membrane fusion.

Refractory pyoderma gangrenosum associated with ulcerative colitis successfully treated with infliximab.

Pyoderma gangrenosum (PG) is a rare, immune-mediated ulcerating skin disease. In up to 50 percent of the cases, PG is associated with underlying systemic disorders, most commonly inflammatory bowel diseases, connective tissue diseases, or hematological disorders. Herein, we present a case of refractory PG associated with ulcerative colitis (UC), successfully treated with infliximab.

Serum albumin levels predict vascular dysfunction with paradoxical pathogenesis in healthy individuals.

BACKGROUND: Serum albumin is affected by both nutritional status and inflammation. It is, therefore, thought to be highly linked with pathogenesis of vascular dysfunction. METHODS: Cross-sectional data from 2091 individuals aged 23-87, who underwent a general health examination, were analyzed. First, we investigated the association between serum albumin level and vascular functions, as assessed by brachial-ankle pulse-wave velocity (PWV). Then, we evaluated the prevalence of hyperglycemia (fasting blood sugar >or=100mg/dl), metabolic syndrome as determined by NCEP criteria, and inflammation (CRP >or=0.4mg/dl), across tertiles of albumin levels. RESULTS: In a multivariate regression model, a U-shaped relationship between serum albumin and PWV was statistically significant when albumin level was treated as a continuous variable in g/dl and centered at 4.4g/dl (quadratic term P-value=0.006). The highest tertile of albumin level (4.6-5.4g/dl) was associated with increased odds ratios for hyperglycemia of 1.35 (1.07-1.70) compared to the middle tertile (4.4-4.5g/dl), whereas the lowest tertile (3.3-4.3g/dl) was associated with reduced odds ratios for hyperglycemia of 0.80 (0.65-0.99). The highest tertile was also associated with increased odds ratios for metabolic syndrome of 1.30 (0.96-1.76) compared to the middle tertile, whereas the lowest tertile was associated with reduced odds ratios of 0.70 (0.51-0.95). Furthermore, the lowest tertile was associated with increased prevalence of inflammation with an adjusted odds ratio of 1.85 (1.15-2.97). CONCLUSIONS: The current results demonstrate that extremes of serum albumin levels are linked to vascular dysfunction among healthy individuals. Furthermore, serum albumin is paradoxically linked to vascular disease under conditions both of overnutrition and of malnutrition and inflammation complex.

Joint effect of alcohol and usual sleep duration on the risk of dysglycemia.

STUDY OBJECTIVES: Sleep duration and alcohol use influence metabolic function. However, limited information exists regarding a combined effect of alcohol and sleep duration on glucose metabolism. The aim of this study was to assess the potential interaction effect of alcohol and inappropriate sleep duration on dysglycemia epidemiologically. DESIGN: Cross-sectional and observational retrospective study. SETTING: A medical health checkup program in a general hospital. PARTICIPANTS: 2933 apparently healthy Japanese individuals, aged 46 to 60 years. INTERVENTION: N/A. MEASUREMENTS AND RESULTS: We examined the relationships between usual sleep duration and dysglycemia, and furthermore assessed the combined effects of alcohol consumption and sleep time on glucose dysmetabolism. A U-shaped relationship between sleep duration and the prevalence of hyperglycemia (fasting plasma glucose level > or =110 mg/dL) was observed when sleep duration was treated as a continuous variables and centered at 7.0 h (quadratic term P = 0.024). In a multivariate quadratic regression model, there was a significant interaction effect between sleep duration and alcohol consumption category (nondrinkers, light-moderate drinkers [ethanol comsumption < or =210 g/wk], and heavy drinkers [ethanol consumption of >210 g/wk]) on fasting plasma glucose levels, with shorter or longer sleep duration being more diabetogenic in individuals who consumed more alcohol (P interaction = 0.018). Furthermore, we found a similar interaction effect of sleep duration and alcohol consumption on the incidence of hyperglycemia during the past 5 years (P interaction = 0.039). CONCLUSION: Alcohol interacts with reduced sleep duration to increase the risk of dysglycemia.

Anoxia/reoxygenation down-regulates the expression of E-cadherin in human colon cancer cell lines.

The E-cadherin-mediated cell-cell adhesiveness is a critical factor for carcinoma cell invasion and metastasis. Anoxia/reoxygenation is known to occur in cancer tissues. In this study, we investigated whether anoxia/reoxygenation induces the down-regulation of E-cadherin expression in the human colon cancer cell lines HT-29, and SW1116. Colon cancer cells were exposed to anoxia (2 h) followed by reoxygenation (4-46 h). The subsequent expression of E-cadherin on the cell surface was examined by immunocytochemistry and enzyme-linked immunosorbent assays, the total amount of E-cadherin protein was examined by Western blotting, and the E-cadherin mRNA level was examined by a real-time polymerase chain reaction assay. The expression of E-cadherin on the cell surface and the total amount of E-cadherin protein were transiently reduced after anoxia/reoxygenation. On the other hand, the E-cadherin mRNA level was not decreased during reoxygenation. Pretreatment with actinomycin D or reagents that interfere with the activation of NF-kappaB significantly attenuated the down-regulation of E-cadherin, which implicated a role for the de novo protein synthesis. These results indicate that anoxia/reoxygenation induces a transient reduction of E-cadherin expression in human colon cancer cells through NF-kappaB dependent transcriptional pathway.

Hypoxia-reoxygenation enhances interleukin-8 production from U937 human monocytic cells.

Hypoxia--reoxygenation (H/R) occurs in both inflammatory spots and tumor tissues, sites in which damage is amplified either acutely or chronically through the infiltration of inflammatory cells. Interleukin-8 (IL-8) is a cytokine with chemotactic and angiogenic properties. This study was designed to investigate the effects of H/R on IL-8 production in the U937 human monocytic cell line. Two hours of hypoxia followed by 4 h of reoxygenation induced a significant increase in IL-8 protein production and IL-8 mRNA expression in U937 cells. Pretreatment with proteasome inhibitor (PSI), a peptide aldehyde known to inhibit the chymotrypsin-like activity of the 26S proteasome specifically, suppressed IL-8 protein production and IL-8 mRNA expression induced by H/R. The production of IL-8 protein induced by H/R was decreased by pioglitazone and 15-deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2)), which have been identified as peroxisome proliferator-activated receptorgamma (PPAR-gamma) ligands. Moreover, transfection of U937 cells with a dominant negative IkappaBalphaexpression vector (IkappaBalphaM) decreased IL-8 protein production induced by H/R. These results suggest that NF-kappaB and PPAR-gamma regulate H/R-stimulated IL-8 production in U937 cells.

Hyperthermia enhances tumor necrosis factor alpha-induced apoptosis of a human gastric cancer cell line.

We have investigated the effects of hyperthermia on the apoptosis induced by tumor necrosis factor alpha (TNF-alpha). Confluent monolayers of human gastric cancer cell line MKN45 were either treated or untreated with hyperthermia for 1 h. The cells were subsequently stimulated with TNF-alpha. A 24-h incubation with TNF-alpha did not affect cell viabilities; however, pretreatment with hyperthermia significantly enhanced the level of apoptosis induced by TNF-alpha. Pretreating MKN45 cells with hyperthermia (42.0 degrees C) significantly inhibited the TNF-alpha-induced increase in the binding activity of NF-kappaB to DNA. This study suggests that hyperthermia can inhibit the TNF-alpha-induced NF-kappaB activation and that hyperthermia renders human gastric cancer cells susceptible to the TNF-alpha-induced apoptosis, possibly via inhibition of the NF-kappaB pathway.

Blocking of NF-kappaB activation enhances the tumor necrosis factor alpha-induced apoptosis of a human gastric cancer cell line.

The transcription factor NF-kappaB is constitutively activated in many human cancers and induces the expression of multiple genes, including those of anti-apoptotic proteins. This study investigated the mechanism by which human gastric cancer cells (MKN45) are resistant to apoptosis induced by tumor necrosis factor alpha (TNF-alpha). Confluent monolayers of MKN45 cells were either pretreated or not for 60 min with PSI, a peptide aldehyde known to specifically inhibit the chymotrypsin-like activity of 26S proteasome. Cells were subsequently stimulated with recombinant human TNF-alpha, and cell viabilities were determined by the WST-1 assay. Apoptosis was confirmed by fluorescence microscopy after staining with Hoechst 33342, and DNA fragmentation was determined by a DNA fragmentation detection kit. A 24-h incubation with either TNF-alpha or PSI alone did not affect cell viabilities; however, pretreatment with PSI significantly enhanced the level of apoptosis induced by TNF-alpha. Therefore, this study suggests the possibility that blocking of NF-kappaB activity renders gastric cancer cells susceptible to the apoptosis induced by TNF-alpha.

Inhibitory effect of polaprezinc on the inflammatory response to Helicobacter pylori.

Helicobacter pylori-infected gastrointestinal mucosa is frequently infiltrated by polymorphonuclear leukocytes (PMN) and monocytes, and these invading cells have been implicated in gastrointestinal mucosal inflammation. To clarify the efficacy of polaprezinc, a chelate compound consisting of zinc and L-carnosine, against H pylori-induced inflammation including PMN infiltration, the in vitro effects of this drug on interleukin (IL)-8 production by an established gastric cancer cell line (MKN 45 cells) and on PMN-endothelial cell adhesive interactions was investigated. Polaprezinc and zinc sulphate inhibited IL-8 production by MKN 45 cells in response to stimulation with H pylori water extract (HPE) in a dose-dependent manner from 10(-7) M to 10(-5) M. In addition, the expression of CD11b and CD18 on PMN and PMN-dependent adhesion to endothelial cells elicited by HPE was inhibited by polaprezinc and zinc sulphate in a concentration-dependent manner. L-carnosine did not have any effects on IL-8 production or PMN-endothelial cell interactions. These results suggest that polaprezinc, mainly the zinc component, may inhibit H pylori-induced PMN-mediated gastric inflammation by attenuating CD11b/CD18 expression on PMN and IL-8 production from gastric epithelial cells.

Inhibitory effects of catechins on neutrophil-dependent gastric inflammation.

The inhibitory effects of tea against carcinogenesis have been attributed to the biological activity of the polyphenol fraction of tea. However, the molecular mechanisms of these effects are not completely understood. Chronic inflammation induced by Helicobacterpylori has been proposed to be a causative pathway in the carcinogenesis of stomach cancer. Therefore, an agent possessing anti-inflammatory properties may be chemopreventative against stomach cancer. In the present study, we have investigated the anti-inflammatory effects of tea catechins. After addition of IL-1beta to MKN45 cells, a gastric cancer cell line, or human umbilical vein endothelial cells (HUVECs), IL-8 production was detected in supernatants. This IL-8 production was inhibited by catechins. Incubation of HUVECs or polymorphonuclear leukocytes (PMNs) with IL-1beta or IL-8, respectively, resulted in an increased surface expression of adhesion molecules. Catechins also inhibited this expression of adhesion molecules on HUVECs and PMNs. Of these major effects, the strongest effect of catechins was to reduce expression of the adhesion molecules CD1lb and CD18 on PMNs. These results suggest that tea may inhibit carcinogenesis partly through the anti-inflammatory effects of tea catechins on PMN-dependent gastric mucosal inflammation.