Association between the Dietary Phytochemical Index and Lower Prevalence of Obesity in Korean Preschoolers.

Little is known regarding Korean preschooler dietary phytochemical index (DPIs). We used the 24 h recall data of 1196 participants aged 3-5 years from the Korea National Health and Nutrition Examination Survey to study the association between dietary food intake and obesity prevalence. The amount of dietary intake by food group was compared according to sex and DPI quartile. Multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression models. The average total DPI and energy from phytochemical food groups were not significantly different according to sex, although boys had a higher total daily food intake. Different inclinations between DPI quartiles and amount of intake were observed in the food groups; specifically, beans showed a higher intake difference between Q1 and Q4 for boys than in the other food groups. The highest DPI quartile had a significantly lower obesity prevalence than the lowest DPI quartile in all models for boys only when obesity prevalence by weight percentile was analyzed (Model 3, OR: 0.287, 95% CI: 0.095-0.868, p for trend < 0.05). Our results suggest a high DPI could help prevent obesity in preschoolers.

Impact of the herbal medicine, Ephedra sinica stapf, on gut microbiota and body weight in a diet-induced obesity model.

Obesity is a chronic metabolic disease caused by excessive body fat and has become a global public health problem. Evidence suggests that obesity and obesity-induced metabolic disorders are closely related to gut microbiota. Bupropion (BP), an antidepressant medicine, and Ephedra sinica Stapf [Ephedraceae; Ephedrae Herba], a herbal medicine, are sympathetic stimulants and have weight loss effects. However, to our best knowledge, no studies have simultaneously assessed the effects of drugs and herbal medicines on obesity and gut microbiota. This study aimed to determine the effects of BP and ES on weight loss and re-modulation of host gut microbiota. To test this hypothesis, we fed C57BL/6J mice with a high-fat diet supplemented with bupropion (BP; 30 mg/kg/day) and Ephedra sinica Stapf extract (ES; 150 mg/kg/day) via oral gavage for eight weeks. Further, we evaluated the effects of BP and ES on body weight and fat accumulation. In addition, we evaluated the effects of BP and ES on gut microbiota using 16S rRNA amplicon sequencing. Our results showed that weight loss was confirmed in both BP and ES; however, it was more pronounced in ES. ES changed the overall composition of the gut microbiota by restoring the relative abundance of Oscillospiraceae, Lachnospiraceae, and the Firmicutes/Bacteroidetes ratio, an indicator of gut microbiota dysbiosis. Nine amplicon sequence variants (ASVs) of the gut microbiome were significantly recovered by BP and ES treatment, of which eight ASVs correlated with body weight and fat accumulation. Additionally, three ASVs were significantly recovered by ES treatment alone. In conclusion, the anti-obesity effects of BP and ES, especially fat accumulation, are related to the regulation of gut microbiota. Moreover, ES had a greater influence on the gut microbiota than BP.

A Clinical Study on the Relationship Among Insomnia, Tongue Diagnosis, and Oral Microbiome.

Currently, there is a lack of adequate methods to assess insomnia objectively. This study addresses the usefulness of tongue features and oral microbial profile as a potential diagnostic biomarker of insomnia. One hundred insomniac patients and 20 healthy control subjects were selected. Their demographic and clinical characteristics, as well as the tongue diagnostic indices and oral microbial profile, were examined. Compared to the control group, insomniac patients showed a higher abnormal low-frequency/high-frequency (LF/HF) ratio. In tongue diagnosis, the indices related to lightness of tongue body and tongue coating were higher in the insomniac group vs. the control group. Furthermore, linear discriminant analysis (LDA) of oral microbial population revealed that the relative abundances of Clostridia, Veillonella, Bacillus and Lachnospiraceae were significantly higher in the insomniac patients than the control group. Additionally, the tongue features of the insomniac group exhibited that the non-coating group had a poor sleep condition compared to the thick-coating group, although the difference was insignificant. On the other hand, the oral microbial communities of the insomniac patients revealed greater alpha and beta diversities in the non-coating group vs. the thick-coating group. The alpha and beta diversities were higher in orotype1 than orotype2. Collectively, this study highlighted that the lightness of tongue body and tongue coating as well as oral microbial profiles of SR1, Actinobacteria, Clostridia and Lachnospiraceae_unclassified could be considered potential biomarkers of insomnia.

Lorcaserin and phentermine exert anti-obesity effects with modulation of the gut microbiota.

Although drugs have been reported to modulate the gut microbiota, the effects of anti-obesity drugs on the gut microbiota remain unclear. Lorcaserin (LS) and phentermine (PT) are commonly used anti-obesity drugs. However, to our best knowledge, no studies have simultaneously assessed the effects of LS and PT on obesity and gut microbiota. This study aimed to explore the relationship between the anti-obesity effects of LS and PT and re-modulation of host gut microbiota. To test hypothesis, we fed C57BL/6J mice with a high-fat diet supplemented with LS and PT via oral gavage for 8 weeks. After sacrifice, body weight, fat accumulation, and serum biomarkers were measured, and the gut microbial composition was analyzed using 16 s rRNA amplicon sequencing. LS and PT were observed to modulate the gut microbial composition and restore gut microbial dysbiosis, as indicated by an increased Firmicutes/Bacteroidetes ratio. Significantly modulated genera by LS and PT treatment were strongly correlated with obesity-related markers. Additionally, LS and PT increased the mRNA level of G protein-coupled receptor 120 (GPR120) in the colon tissue. ASV3566, which corresponds to Eubacterium coprostanoligenes, was correlated with GPR120 and obesity-related markers such as glutamic pyruvic transaminase (GPT) and serum triglyceride (TG). In conclusion, LS and PT can modulate the gut microbiota dysbiosis and the gut microbiota plays a role in mediating the anti-obesity effect of drugs.

Anti-Obesity Effect of Fermented Panax notoginseng Is Mediated Via Modulation of Appetite and Gut Microbial Population.

Panax notoginseng (PN) is a traditional herbal medicine containing several active compounds such as saponins and ginsenosides with many therapeutic applications including anti-obesity activity. Fermentation by lactic acid bacteria has the potential to metabolize ginsenosides to more active forms. This study examined whether fermentation has any benefits on the protective effects of a PN extract against obesity using a high-fat diet (HFD)-fed mouse model. PN was fermented with Lactobacillus plantarum which exhibited high ß-glucosidase activity. Upon fermentation, the PN extract exhibited an altered ginsenoside profile, a dramatic increase in the lactate level. Treatment of the HFD group with fermented PN (FPN), but not PN, decreased both the food and calorie intake significantly, which was consistent with the more potent suppressing effects of FPN than PN on the signaling pathways involved in appetite and energy intake. The PN treatment also modulated the gut microbial composition. The PN and FPN treatment groups showed clear differences in the population of gut microbiota. The relative abundance of Bacteroidetes, Erysipelotrichaceae, Coprococus, and Dehalobacterium were significantly higher in the FPN group then the normal, HFD, and XEN groups. Furthermore, the relative abundances of Akkermansia, Dehalobacterium, Erysipeliotrichaceae and parpabacteroides were significantly higher in the FPN group than the PN group, but the relative abundances of Allobaculum, Erysipelotrichi and Erysipelotrichale were significantly lower. The relative abundance of Bacteroides and Lactococcus was significantly higher and lower, respectively in the PN and FPN groups than the HFD group. In conclusion, the altered ginsenoside and organic acid's profile, and altered gut microbial composition are believed to be the major factors contributing to the anti-obesity properties of FPN.

Fibrinogen-Like Protein 1 Modulates Sorafenib Resistance in Human Hepatocellular Carcinoma Cells.

Despite liver cancer being the second-leading cause of cancer-related death worldwide, few systemic drugs have been approved. Sorafenib, the first FDA-approved systemic drug for unresectable hepatocellular carcinoma (HCC), is limited by resistance. However, the precise mechanisms underlying this phenomenon are unknown. Since fibrinogen-like 1 (FGL1) is involved in HCC progression and upregulated after anticancer therapy, we investigated its role in regulating sorafenib resistance in HCC. FGL1 expression was assessed in six HCC cell lines (HepG2, Huh7, Hep3B, SNU387, SNU449, and SNU475) using western blotting. Correlations between FGL1 expression and sorafenib resistance were examined by cell viability, colony formation, and flow cytometry assays. FGL1 was knocked-down to confirm its effects on sorafenib resistance. FGL1 expression was higher in HepG2, Huh7, and Hep3B cells than in SNU387, SNU449, and SNU475 cells; high FGL1-expressing HCC cells showed a lower IC50 and higher sensitivity to sorafenib. In Huh7 and Hep3B cells, FGL1 knockdown significantly increased colony formation by 61% (p = 0.0013) and 99% (p = 0.0002), respectively, compared to that in controls and abolished sorafenib-induced suppression of colony formation, possibly by modulating ERK and autophagy signals. Our findings demonstrate that sorafenib resistance mediated by FGL1 in HCC cells, suggesting FGL1 as a potential sorafenib-resistance biomarker and target for HCC therapy.

The Herbal Formula CWBSD Improves Sleep Quality Dependent on Oral Microbial Type and Tongue Diagnostic Features in Insomnia.

Cheonwangbosim-dan (CWBSD) is a traditional Korean herb formula that has been widely prescribed for insomnia patients with a heart-yin deficiency (HYD) pattern. Several studies have reported that heart function and insomnia are interrelated, and few have explored associations between insomnia, oral microbiota, and tongue diagnosis. This study aimed to evaluate the effects of CWBSD on primary insomnia, tongue diagnosis, and oral microbiota. At baseline, 56 patients with primary insomnia were assigned to two groups, a HYD group and a non-HYD (NHYD) group and they took CWBSD for 6 weeks. During the study, Pittsburgh Sleep Quality Indices (PSQIs) and Insomnia Severity Indices (ISIs) decreased significantly in both groups. However, the PSQI reduction observed in the HYD group was greater than in the NHYD group and sleep times increased only in the HYD group. As sleep quality improved, the amount of tongue coating increased at the posterior tongue, where heart function appears. At baseline, the HYD and NHYD group had a specific oral microbiota (Veillonella at genus level), but no significant change was observed after taking CWBSD. Additionally, subjects were divided into two oral microbiota types ("orotypes"). The genera Prevotella, Veillonella, or Neisseria were abundant in each orotype. The reduction in PSQI in orotype 1 during the 6-week treatment period was greater than in orotype 2. In conclusion, this study shows that CWBSD could be used to treat primary insomnia in patients with a HYD pattern as determined using tongue diagnosis and oral microbiota distributional patterns.

Inhibition of Colony-Stimulating Factor 1 Receptor by PLX3397 Prevents Amyloid Beta Pathology and Rescues Dopaminergic Signaling in Aging 5xFAD Mice.

Alzheimer's disease (AD) is a progressive neurodegenerative disease. In this study, to investigate the effect of microglial elimination on AD progression, we administered PLX3397, a selective colony-stimulating factor 1 receptor inhibitor, to the mouse model of AD (5xFAD mice). Amyloid-beta (Aß) deposition and amyloid precursor protein (APP), carboxyl-terminal fragment ß, ionized calcium-binding adaptor molecule 1, synaptophysin, and postsynaptic density (PSD)-95 levels were evaluated in the cortex and hippocampus. In addition, the receptor density changes in dopamine D2 receptor (D2R) and metabotropic glutamate receptor 5 were evaluated using positron emission tomography (PET). D2R, tyrosine hydroxylase (TH), and dopamine transporter (DAT) levels were analyzed in the brains of Tg (5xFAD) mice using immunohistochemistry. PLX3397 administration significantly decreased Aß deposition following microglial depletion in the cortex and hippocampus of Tg mice. In the neuro-PET studies, the binding values for D2R in the Tg mice were lower than those in the wild type mice; however, after PLX3397 treatment, the binding dramatically increased. PLX3397 administration also reversed the changes in synaptophysin and PSD-95 expression in the brain. Furthermore, the D2R and TH expression in the brains of Tg mice was significantly lower than that in the wild type; however, after PLX3397 administration, the D2R and TH levels were significantly higher than those in untreated Tg mice. Thus, our findings show that administering PLX3397 to aged 5xFAD mice could prevent amyloid pathology, concomitant with the rescue of dopaminergic signaling, suggesting that targeting microglia may serve as a useful therapeutic option for neurodegenerative diseases, including AD.

Genome­wide analysis of DNA methylation and gene expression changes in an ovalbumin­induced asthma mouse model.

The aim of the present study was to establish an integrated network of DNA methylation and RNA expression in an ovalbumin (OVA)­induced asthma model, and to investigate the epigenetically­regulated genes involved in asthma development. Genome­wide CpG­DNA methylation profiling was conducted through the use of a methylated DNA immunoprecipitation microarray and RNA sequencing was performed using three lung samples from mice with OVA­induced asthma. A total of 35,401 differentially methylated regions (DMRs) were identified between mice with OVA­induced asthma and control mice. Of these, 3,060 were located in promoter regions and 370 of the genes containing these DMRs demonstrated an inverse correlation between methylation and gene expression. Kyoto Encyclopedia of Genes and Genomes pathway analysis identified that 368 genes were upregulated or downregulated in OVA­induced asthma samples, including genes involved in 'chemokine signalling pathway', 'focal adhesion', 'leukocyte transendothelial migration' and 'vascular smooth muscle contraction signaling' pathways. Integrated network analysis identified four hub genes, consisting of three upregulated genes [forkhead box O1 (FOXO1), SP1 transcription factor (SP1) and amyloid ß precursor protein (APP)], and one downregulated gene [RUNX family transcription factor 1 (RUNX1)], all of which demonstrated an association between DNA methylation and gene expression. These genes were highly interconnected nodes in the Ingenuity Pathway Analysis module and were functionally significant. A total of four interconnected hub genes, FOXO1, RUNX1, SP1 and APP, were identified from the integrated DNA methylation and gene expression networks involved in asthma development. These results suggested that modulating these four genes could effectively control the development of asthma.

Chemically or surgically induced thyroid dysfunction altered gut microbiota in rat models.

Thyroid hormones are essential for the regulation of energy homeostasis and metabolic processes. However, the relationship between thyroid function and host gut microbial communities is not properly understood. To determine whether and how gut microbiota is associated with thyroid function, metagenomics analysis of the bacterial population in fecal samples of rat models of hyperthyroidism (induced by levothyroxine) and hypothyroidism (induced by propylthiouracil or thyroidectomy) was conducted through 16S rRNA gene sequencing. Our results revealed that all thyroid dysfunction models were definitely established and gut microbial composition varied according to different thyroid functional status. The relative abundance of Ruminococcus was significantly higher in the hyperthyroidism group (HE) vs both the normal and hypothyroidism groups (HO) while S24-7 was significantly higher in the HO group. The population of Prevotellaceae and Prevotella were significantly lower in the HO group vs the normal. Firmicutes and Oscillospira were significantly higher in the SHO (surgery-induced hypothyroidism) group, while Prevotellaceae and Prevotella showed lower abundance in the SHO group than the SHAM group. Present results suggest that thyroid functions may have the potential to influence the profile of gut microbiota and could be used as foundation to investigate interaction mechanism between thyroid and gut microbiome.

Silibinin Attenuates Silica Dioxide Nanoparticles-Induced Inflammation by Suppressing TXNIP/MAPKs/AP-1 Signaling.

Silica dioxide nanoparticles (SiONPs) have been applied to several fields, such as drug delivery and gene therapy. However, SiONPs are a constituent of fine dust and can induce excessive inflammatory responses in the lungs via the airways. Silibinin, a major component of silymarin, has been known for its anti-oxidant and anti-inflammatory effects. In the present study, we explored the protective effects of silibinin against SiONPs-induced airway inflammation and explored its underlying mechanism of action, focusing on thioredoxin-interacting protein (TXNIP)/mitogen-activated protein kinases (MAPKs) in vitro and in vivo. In SiONPs-stimulated NCI-H292 airway epithelial cells, silibinin treatment effectively suppressed the elevation of the mRNA expression of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1ß, which was accompanied by the reduction in the expression of TXNIP, MAPKs, and activator protein-1 (AP-1). In SiONPs-treated mice, silibinin administration inhibited the increase in inflammatory cell counts and proinflammatory mediators, and it alleviated airway inflammation by SiONPs exposure. In addition, silibinin administration effectively suppressed the elevation of TXNIP/MAPKs/AP-1 signaling by SiONPs exposure. Taken together, silibinin effectively inhibited SiONPs-induced inflammatory responses, and this effect was closely related to the inhibition of TXNIP/MAPK/AP-1 signaling. These results suggested that silibinin might be useful for reducing pulmonary inflammation induced by SiONPs.

Silica dioxide nanoparticles aggravate airway inflammation in an asthmatic mouse model via NLRP3 inflammasome activation.

Silica dioxide nanoparticles (SiONPs) are mainly used in the rubber industry; however, they are a major air pollutant in Asia. Thus, extensive research on this issue is required. In this study, we investigated the effects of SiONPs on asthma aggravation and elucidated the underlying mechanism using ovalbumin (OVA)-induced asthmatic mice model and in NCI-H292 cells. Mice exposed to SiONPs showed markedly increased Penh values, inflammatory cell counts, and inflammatory cytokine levels compared to OVA-induced asthmatic mice. Exposure to SiONPs also induced additional airway inflammation and mucus secretion with increases in protein expression levels of thioredoxin-interacting protein (TXNIP), NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome, and interleukin (IL)-1ß compared to those in OVA-induced asthmatic mice. Treatment of SiONPs in NCI-H292 cells also significantly increased mRNA expression levels of inflammatory cytokines accompanied with elevation in the levels of TXNIP, NLRP3 inflammasome, and IL-1ß proteins in a concentration-dependent manner. Taken together, exposure to SiONPs aggravated asthma development, which is closely related to inflammasome activation. Our results provide useful information about the toxicological effects of SiONPs on asthma exacerbation and suggest the need to avoid SiONP exposure especially in individuals with respiratory diseases.

Scrophularia koraiensis Nakai Attenuates Allergic Airway Inflammation via Suppression of NF-κB and Enhancement of Nrf2/HO-1 Signaling.

Scrophularia koraiensis Nakai (Scrophulariaceae) is a medicinal herb that grows in Korea and which has been widely used to treat fever, edema, neuritis and laryngitis. Hence, we evaluated the anti-inflammatory and antioxidant effects of the ethanol extract (SKE) of S. koraiensis Nakai in an ovalbumin (OVA)-induced mouse model. We injected 20 µg of OVA with 2 mg of aluminum on day 0 and day 14 to induce allergic airway inflammation in six-week-old BALB/c mice, and mice were challenged with 1% OVA by nebulization for 1 h on days 21, 22, and 23. SKE was orally administered at 20 mg/kg and 40 mg/kg from day 18 to 23, and its effects were compared with those of montelukast treatment. SKE significantly reduced proinflammatory cytokines, inflammatory cell counts, immunoglobulin-E, and airway hyperresponsiveness during the OVA-induced allergic airway inflammation model; it also reduced airway inflammation and mucus production. In addition, SKE reduced the OVA-induced nuclear factor kappa B (NF-κB) phosphorylation in lung tissues while enhancing nuclear factor erythroid-derived 2-related factor (Nrf-2) and heme oxygenase-1 (HO-1) expression. In conclusion, SKE showed the protective effects on OVA-induced allergic airway inflammation via the suppression of NF-κB phosphorylation and the enhancement of the Nrf2/HO-1 signaling pathway. These results indicate that SKE is a potential therapeutic agent for allergic airway inflammation.

Lactate-Fortified Puerariae Radix Fermented by Bifidobacterium breve Improved Diet-Induced Metabolic Dysregulation via Alteration of Gut Microbial Communities.

BACKGROUND: Puerariae Radix (PR), the dried root of Pueraria lobata, is reported to possess therapeutic efficacies against various diseases including obesity, diabetes, and hypertension. Fermentation-driven bioactivation of herbal medicines can result in improved therapeutic potencies and efficacies. METHODS: C57BL/6J mice were fed a high-fat diet and fructose in water with PR (400 mg/kg) or PR fermented by Bifidobacterium breve (400 mg/kg) for 10 weeks. Histological staining, qPCR, Western blot, and 16s rRNA sequencing were used to determine the protective effects of PR and fermented PR (fPR) against metabolic dysfunction. RESULTS: Treatment with both PR and fPR for 10 weeks resulted in a reduction in body weight gain with a more significant reduction in the latter group. Lactate, important for energy metabolism and homeostasis, was increased during fermentation. Both PR and fPR caused significant down-regulation of the intestinal expression of the MCP-1, IL-6, and TNF-α genes. However, for the IL-6 and TNF-α gene expressions, the inhibitory effect of fPR was more pronounced (p < 0.01) than that of PR (p < 0.05). Oral glucose tolerance test results showed that both PR and fPR treatments improved glucose homeostasis. In addition, there was a significant reduction in the expression of hepatic gene PPARγ, a key regulator of lipid and glucose metabolism, following fPR but not PR treatment. Activation of hepatic AMPK phosphorylation was significantly enhanced by both PR and fPR treatment. In addition, both PR and fPR reduced adipocyte size in highly significant manners (p < 0.001). Treatment by fPR but not PR significantly reduced the expression of PPARγ and low-density lipoproteins in adipose tissue. CONCLUSION: Treatment with fPR appears to be more potent than that of PR in improving the pathways related to glucose and lipid metabolism in high-fat diet (HFD)+fructose-fed animals. The results revealed that the process of fermentation of PR enhanced lactate and facilitated the enrichment of certain microbial communities that contribute to anti-obesity and anti-inflammatory activities.

Scrophularia buergeriana attenuates allergic inflammation by reducing NF-κB activation.

BACKGROUND: Scrophularia buergeriana Miq. (Scrophulariaceae) (SB) has been used as an oriental medicine for the treatment of inflammatory diseases, such as neuritis and pharyngolaryngitis. PURPOSE: We explored the therapeutic effects of S. buergeriana ethanol extract (SBE) on airway inflammation in ovalbumin (OVA)-induced asthmatic mice and lipopolysaccharide (LPS)-stimulated RAW264.7 cells. METHODS: Mice were intraperitoneally injected with OVA on days 0 and 14 to elevate the immune response. On days 21 to 23, the mice were challenged with OVA solution and SBE (20 and 40 mg/kg) was administered daily by oral gavage from days 18 to 23. RAW264.7 cells were pretreated with SBE 1 h before LPS stimulation. RESULTS: SBE administration effectively suppressed inflammatory cell infiltration, the expression of interleukin (IL)-5, IL-13, and IL-17, immunoglobulin E, and airway hyperresponsiveness in an OVA-induced allergic asthma model. A reduction in histological alterations, including airway inflammation and mucus hypersecretion, was observed. These effects of SBE were accompanied by a decrease in matrix metalloproteinase-9 (MMP-9) expression and nuclear factor kappa B (NF-κB) phosphorylation. These responses were observed in LPS-stimulated RAW264.7 cells. SBE treatment reduced the mRNA expression of tumor necrosis factor (TNF)-α, IL-6, and MMP-9, and NF-κB phosphorylation, in LPS-stimulated RAW264.7 cells. CONCLUSION: Our results indicated that SBE effectively attenuated airway inflammation in an OVA-induced allergic asthma model. These properties of SBE were thought to be involved in the suppression of NF-κB phosphorylation, suggesting that the material has the potential to regulate the development of allergic asthma.

Combined effects of Scutellaria baicalensis with metformin on glucose tolerance of patients with type 2 diabetes via gut microbiota modulation.

Metformin is a widely prescribed antidiabetic agent, whereas Scutellaria baicalensis (SB) is a commonly used medicinal herb for treatment of type 2 diabetes (T2D). Gut microbiota is involved in pathophysiology of metabolic diseases including T2D, and intestinal microbiota may be one of the important therapeutic targets for the ailment. This study was conducted to investigate the effects of SB combined with metformin on treatment of T2D while evaluating changes in the gut microbiota composition. Patients with T2D were randomized into control and treatment groups. Subjects who had already been prescribed metformin were allotted to additional SB (3.52 g/day) group or placebo group. The initial treatment session was 8 wk, and after washout period for 4 wk they were crossed over to the opposite treatment for another 8 wk. The influence of SB and placebo on the intestinal microbiota was analyzed by MiSeq system based on 16S rRNA gene. Glucose tolerance was lower in the SB group than the placebo group. Similarly, the relative RNA expression of TNF-α was significantly reduced after SB treatment. SB treatment influenced the gut microbiota, especially Lactobacillus and Akkermansia, which showed remarkable increases after SB treatment. Some subjects showed high liver enzyme levels after SB treatment, and their microbiota composition at baseline differed with subjects whose liver enzymes were not affected. We also predicted that selenocompound metabolism was increased and naphthalene degradation was decreased after SB treatment. These results suggest that SB with metformin treatment may improve the glucose tolerance and inflammation and influence the gut microbiota community in T2D.

Role of melatonin as an SIRT1 enhancer in chronic obstructive pulmonary disease induced by cigarette smoke.

BACKGROUND: Melatonin has various biological activities that improve the health of an individual. We evaluated the effects of melatonin on inflammatory response in chronic obstructive pulmonary disease (COPD), focusing on the regulation of SIRT1 expression. METHODS: To investigate the effect of melatonin, we used cigarette smoke (CS)-induced COPD mouse model and CS condensate (CSC)-stimulated J774 macrophage cells. RESULTS: CSC-stimulated J774 macrophages exhibited increased p65 acetylation with a reduction in SIRT1 expression. However, melatonin induced the enhancement of SIRT1 expression, which eventually decreased p65 acetylation in CSC-stimulated J774 cells. Melatonin-treated mice exhibited an enhancement in SIRT1 expression with the reduction in p65 acetylation, which decreased the level of inflammatory mediators induced by CS. Additionally, SIRT1 inhibitor treatment increased the level of inflammatory mediators, which was accompanied by an increase in p65 acetylation. However, cotreatment with melatonin and an SIRT1 inhibitor reduced the level of inflammatory mediators compared with that by treatment with the SIRT1 inhibitor alone, which was accompanied by elevation in SIRT1 expression and reduction in p65 acetylation. CONCLUSIONS: Overall, the results indicated that melatonin has therapeutic effects against COPD, owing to its property to enhance SIRT1 expression.

4-Hydroxycinnamic acid suppresses airway inflammation and mucus hypersecretion in allergic asthma induced by ovalbumin challenge.

In this study, we investigated whether 4-hydroxycinnamic acid (HA) has a palliative effect on asthmatic inflammatory responses using a mouse model of ovalbumin (OVA)-induced allergic asthma. The mice were divided into five groups, each consisting of seven females (normal control phosphate-buffered saline); OVA (OVA sensitization/challenge); dexamethasone (DEX, OVA sensitization/challenge + dexamethasone 3 mg/kg); HA-10 and HA-20 OVA sensitization/challenge + HA 10 and 20 mg/kg, respectively). Mice treated with HA showed a reduction in airway hyperresponsiveness and in the number of inflammatory cells in bronchoalveolar lavage fluid (BALF) compared with asthmatic control. HA treatment also reduced the levels of interleukin (IL)-5 and IL-13 in BALF and of OVA-specific immunoglobulin E in the serum compared with asthmatic control. HA treatment relieved airway inflammation and mucus overproduction caused by OVA exposure. Additionally, HA inhibited the increases in levels of nuclear factor kappa B, inducible nitric oxide synthase, and cyclooxygenase-2 that normally occur after OVA exposure. HA treatment also reduced the activity and protein level of matrix metalloproteinase-9. Taken together, HA effectively suppressed asthmatic airway inflammation and mucus production caused by OVA exposure. These findings indicate that HA has the potential to be used as a therapeutic agent for asthma.

Cisplatin-induced ototoxicity involves interaction of PRMT3 and cannabinoid system.

This study investigated whether protein arginine methyltransferase (PRMT) and the cannabinoid system are involved in cisplatin-induced ototoxicity. Cisplatin increased cytosine-cytosine-adenosine-adenosine-thymidine-enhancer-binding protein homologous protein expression. This effect is indicative of an increase in endoplasmic reticulum (ER) stress, and apoptosis signaling including cleavage of caspase-3, caspase-9, poly-adenosine diphosphate-ribose polymerase, and phospho-p53, as well as expression of PRMT3, PRMT4 and fatty acid amide hydrolase (FAAH)1 in House Ear Institute-Organ of Corti 1 (HEI-OC1) cells. In addition, overexpression of PRMT3 or PRMT4 increased the expression of FAAH1 expression, apoptosis, and ER stress signaling in HEI-OC1 cells, whereas PRMT3 or PRMT4 knockdown had the opposite effect. Furthermore, overexpression of FAAH1 increased apoptosis and ER stress, but expression of the PRMTs was unchanged. In addition, a cannabinoid 1 receptor agonist and FAAH inhibitor attenuated apoptosis and ER stress, while cisplatin increased the binding of PRMT3 with FAAH1. In the in vivo experiments, cisplatin was injected intraperitoneally at 6 mg/kg/day into C57BL/6 mice, and 7 days later, this study confirmed that PRMT3 and PRMT4 were upregulated in the organ of Corti of the mice. These results indicate that cisplatin-induced ototoxicity was correlated with PRMT3, PRMT4 and the cannabinoid system, and PRMT3 binding with FAAH1 was increased by cisplatin in HEI-OC1 cells. Therefore, this study suggests that PRMT3 mediates cisplatin-induced ototoxicity via interaction with FAAH1 in vitro and in vivo.

Diet Control More Intensively Disturbs Gut Microbiota Than Genetic Background in Wild Type and ob/ob Mice.

Changes in environmental and genetic factors are vital to development of obesity and its complications. Induction of obesity and type 2 diabetes by both leptin deficiency (ob/ob) and high fat diet (HFD) has been verified in animal models. In the present experiment, three types of diets (normal diet; ND, HFD and high sucrose diet; HSD) and two types of genetic mice (Wild type: WT and ob/ob) were used to explore the relationship among diet supplements, gut microbiota, host genetics and metabolic status. HFD increased the body, fat and liver weight of both ob/ob and WT mice, but HSD did not. HFD also resulted in dyslipidemia, as well as increased serum transaminases and fasting glucose in ob/ob mice but not in WT mice, while HSD did not. Moreover, HFD led to brain BDNF elevation in WT mice and reduction in ob/ob mice, whereas HSD did not. Both HFD and HSD had a greater influence on gut microbiota than host genotypes. In detail, both of HFD and HSD alteration elucidated the majority (≥63%) of the whole structural variation in gut microbiota, however, host genetic mutation accounted for the minority (≤11%). Overall, diets more intensively disturbed the structure of gut microbiota in excess of genetic change, particularly under leptin deficient conditions. Different responses of host genotypes may contribute to the development of metabolic disorder phenotypes linked with gut microbiota alterations.