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.

Nanoscale Mapping of Carrier Mobilities in the Ballistic Transports of Carbon Nanotube Networks.

Much progress has been made in the nanoscale analysis of nanostructures, while the mapping of key charge transport properties such as a carrier mobility remains a challenge, especially for one-dimensional systems. Here, we report the nanoscale mapping of carrier mobilities in carbon nanotube (CNT) networks and show that charge transport behaviors varied depending on network structures. In this work, the spatial distribution of localized charge transport properties such as mobilities and charge trap densities in CNT networks were mapped via a scanning noise microscopy. The mobility map was obtained from the conductivity maps measured at different back-gate biases, showing up to two orders of mobility variations depending on localized network structures. Furthermore, from the maps, correlations between mobility/conductivity and charge trap density were analyzed to determine charge transport mechanisms. In metallic CNT networks, the regions with rather high (low) or low (high) charge trap densities (mobilities) exhibited a diffusive or ballistic transport behavior, respectively. Interestingly, semiconducting CNT networks also exhibited a gradual transition from a diffusive to a ballistic transport behavior as the CNT mobility was increased by reaching the on-state with negative gate biases. The mapping of the cross-patterned CNT network showed that metallic CNT electrodes could achieve a good electrical contact with semiconducting CNTs without high contact resistance regions. Since this method allowed one to map versatile charge transport properties such as mobility, conductivity, and charge trap density, it can be a powerful tool for basic research about charge transport phenomena and practical device applications.

Frequency-Dependent Effects on Coordination and Prefrontal Hemodynamics During Finger Force Production Tasks.

Behavioral stability partially depends on the variability of net outcomes by means of the co-varied adjustment of individual elements such as multi-finger forces. The properties of cyclic actions affect stability and variability of the performance as well as the activation of the prefrontal cortex that is an origin of subcortical structure for the coordinative actions. Little research has been done on the issue of the relationship between stability and neuronal response. The purpose of the study was to investigate the changes in the neural response, particularly at the prefrontal cortex, to the frequencies of isometric cyclic finger force production. The main experimental task was to produce finger forces while matching the produced force to sine-wave templates as accurately as possible. Also, the hemodynamics responses of the prefrontal cortex, including oxy-hemoglobin concentration (ΔHbO) and the functional connectivity, were measured using functional near-infrared spectroscopy. The frequency conditions comprised 0.1, 1, and 2 Hz. The uncontrolled manifold (UCM) approach was applied to compute synergy indices in time-series. The relative phase (RP), the coefficient of variation (CV) of the peak and trough force values were computed as the indices of performance accuracy. The statistical parametric mapping (SPM) was implemented to compare the synergy indices of three frequency conditions in time-series. A less accurate performance in the high-frequency condition was caused not by the RP, but mainly by the inconsistent peak force values (CV; p < 0.01, η p 2 = 0.90). The SPM analysis revealed that the synergy indices were larger in the low-frequency than in high-frequency conditions. Further, the ΔHbO remained unchanged under all frequency conditions, while the functional connectivity decreased with an increase in the frequency of cyclic force production. The current results suggested that the concurrent activation of the prefrontal region mainly depends on the frequency of cyclic force production, which was associated with the strength of stability indices and performance errors. The current study is the first work to uncover the effect of frequency on the multi-finger synergies as to the hemodynamic response in the prefrontal cortex, which possibly provides a clue of the neural mechanism of synergy formation and its changes.

Changes in intersegmental stability during gait in patients with spastic cerebral palsy.

BACKGROUND: Dysfunction in peripheral and neural structure with spastic cerebral palsy (CP) causes impaired performance and stability of various behaviors. Recent progress of quantification methods for the stability properties, which is based on the uncontrolled manifold hypothesis, has been applied to various neurological disorders. A prior study revealed that the ability for purposeful regulation of stability properties is weakened with CP during finger and hand actions. Successive regulation of stability properties is crucial for human locomotion; therefore, it is imperative to quantify the changes in the intersegmental coordination as to the stable performance in CP individuals during gait. RESEARCH QUESTION: We hypothesized that (1) Spastic CP group will show smaller step length and gait velocity with larger variability, and (2) Spastic CP group will show no changes in average stability indices for both the COM and head position stabilization, while the smaller difference between stable and unstable posture during the gait cycle. METHODS: Whole-body kinematic data during walking were collected from CP and control subjects. Step length, velocity, and coefficient of variation (CV) were calculated as spatiotemporal parameters. We quantified the intersegmental stability index in time-series during gait for the stabilization of the whole-body COM and head position. RESULTS: The CP subjects showed smaller step length and velocity with larger CV than the controls. However, the CP group showed a significantly less difference in the stability indices between the single- and double-limb support phases as compared to the controls for both the COM and head position stabilization. SIGNIFICANCE: Present study is the first to document the quantification of changing intersegmental stability in the spastic CP during locomotion. The dysfunction of intentional modulation of stability properties in CP individuals may be a more common problem, which is not limited to a specific body effector.

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.

Bioelectronic Skin Based on Nociceptive Ion Channel for Human-Like Perception of Cold Pains.

A bioelectronic skin device based on nociceptive ion channels in nanovesicles is developed for the detection of chemical cold-pain stimuli and cold environments just like human somesthetic sensory systems. The human transient receptor potential ankyrin 1 (hTRPA1) is involved in transmission and modulation of cold-pain sensations. In the bioelectronic skin, the nanovesicles containing the hTRPA1 nociceptive ion channel protein reacts to cold-pain stimuli, and it is electrically monitored through carbon nanotube transistor devices based on floating electrodes. The bioelectronic skin devices sensitively detect chemical cold-pain stimuli like cinnamaldehyde at 10 fm, and selectively discriminate cinnamaldehyde among other chemical stimuli. Further, the bioelectronic skin is used to evaluate the effect of cold environments on the response of the hTRPA1, finding that the nociceptive ion channel responds more sensitively to cinnamaldehyde at lower temperatures than at higher temperatures. The bioelectronic skin device could be useful for a basic study on somesthetic systems such as cold-pain sensation, and should be used for versatile applications such as screening of foods and drugs.

Micelle-stabilized Olfactory Receptors for a Bioelectronic Nose Detecting Butter Flavors in Real Fermented Alcoholic Beverages.

A bioelectronic nose device based on micelle-stabilized olfactory receptors is developed for the selective discrimination of a butter flavor substance in commercial fermented alcoholic beverages. In this work, we have successfully overexpressed ODR-10, a type of olfactory receptor, from Caenorhabditis elegans using a bacterial expression system at a low cost and high productivity. The highly-purified ODR-10 was stabilized in micelle structures, and it was immobilized on a carbon nanotube field-effect transistor to build a bioelectronic nose for the detection of diacetyl, a butter flavor substance, via the specific interaction between diacetyl and ODR-10. The bioelectronic nose device can sensitively detect diacetyl down to 10 fM, and selectively discriminate it from other substances. In addition, this sensor could directly evaluate diacetyl levels in a variety of real fermented alcoholic beverages such as beer, wine, and makgeolli (fermented Korean wine), while the sensor did not respond to soju (Korean style liquor without diacetyl). In this respect, our sensor should be a powerful tool for versatile food industrial applications such as the quality control of alcoholic beverages and foods.

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.

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.

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.

Melatonin attenuates cisplatin-induced acute kidney injury in rats via induction of anti-aging protein, Klotho.

This study investigated the protective effects of melatonin (MT) against cisplatin (CP)-induced acute kidney injury in rats as well as its possible mechanism of action associated with anti-aging protein Klotho. The following four experimental groups were evaluated: vehicle control, CP (7 mg/kg), CP&MT20 (20 mg/kg/day), and CP&MT40 (40 mg/kg/day). The concomitant administration of MT significantly ameliorated CP-induced acute kidney injury in rats, as evidenced by increased kidney weight, increased serum levels of blood urea nitrogen and creatinine, and increased incidence of histopathological alterations with renal tubular cell apoptosis. In addition, MT treatment protected kidney tissue against oxidative damages and significantly upregulated the expression level of Klotho decreased by CP treatment, resulting in reduced phosphorylation of protein kinase B (AKT) and forkhead box O (FOXO) as well as reduced expression levels of B-cell lymphoma 2-associated X protein (Bax) and caspase-3. MT not only partially regulated oxidative stress via AKT/FOXO signaling, but also reduced apoptosis caused by CP by inhibiting the Bax/caspase-3 pathway. Our results indicated that MT could prevent acute kidney injury induced by CP in rats, presumably through upregulating the expression of Klotho, resulting in elevated anti-oxidant and anti-apoptotic properties.

Therapeutic Effect of Dipsacus asperoides C. Y. Cheng et T. M. Ai in Ovalbumin-Induced Murine Model of Asthma.

Dipsacus asperoides C. Y. Cheng et T. M. Ai (DA) has been used in China as a traditional medicine to treat lumbar and knee pain, liver dysfunction, and fractures. We explored the suppressive effect of DA on allergic asthma using an ovalbumin (OVA)-induced asthma model. In the asthma model, female Balb/c mice were sensitized to OVA on day 0 and 14 to boost immune responses and then exposed to OVA solution by using an ultrasonic nebulizer on days 21 to 23. DA (20 and 40 mg/kg) was administered to mice by oral gavage on days 18 to 23. Methacholine responsiveness was determined on day 24 using a plethysmography. On day 25, we collected bronchoalveolar lavage fluid, serum, and lung tissue from animals under anesthesia. DA treatment effectively inhibited methacholine responsiveness, inflammatory cell infiltration, proinflammatory cytokines such as interleukin (IL)-5 and IL-13, and immunoglobulin (Ig) E in OVA-induced asthma model. Reductions in airway inflammation and mucus hypersecretion, accompanied by decreases in the expression of inducible nitric oxide synthase (iNOS) and the phosphorylation of nuclear factor kappa B (NF-κB), were also observed. Our results indicated that DA attenuated the asthmatic response, and that this attenuation was closely linked to NF-κB suppression. Thus, this study suggests that DA is a potential therapeutic for allergic asthma.

Modificated Mahuang-Tang, a traditional herbal medicine suppresses inflammatory responses induced by cigarette smoke in human airway epithelial cell and mice.

BACKGROUND: Cigarette smoke (CS) is a major contributor to the high incidence of chronic obstructive pulmonary disease (COPD) featured as chronic inflammation and airway obstruction. Mahuang-Tang is a traditional polyherbal mixture composed of four different herbs. It is widely used in Asia as a remedy for allergic reaction and inflammation. PURPOSE: We investigated the effects of a modificated Mahuang-Tang water extract (MTWE) against airway inflammation caused by CS and lipopolysaccharide (LPS) in mice and cigarette smoke condensate (CSC)-stimulated NCI-H292 cells. METHODS: CS exposed to animals for 1 h per day from day 1 to day 7 and treated with LPS intranasally on day 4. One hour before CS exposure, animals were received MTWE (50 or 100 mg/kg) by oral gavage. Inflammatory cell count and cytokines levels were measured in the bronchoalveolar lavage fluid. Expression levels of matrix metalloprotease-9 (MMP-9) and extracellular signal-regulated kinase (Erk) were analyzed by western blotting. RESULTS: MTWE markedly decreased the neutrophil and other inflammatory cell counts in the bronchoalveolar lavage fluid and reduced proinflammatory mediators as evidenced by the decreases in inflammatory cell recruitment in lung tissue. Furthermore, MTWE meaningfully declined MMP-9 expression and reduced the Erk phosphorylation, caused by the CS and LPS exposure. In in vitro experiments, MTWE suppressed the elevated expression of proinflammatory cytokines induced by CSC treatment. MTWE reduced Erk phosphorylation and MMP-9 expression in CSC-stimulated H292 cells. CONCLUSION: Overall, MTWE effectively inhibited the pulmonary inflammation and MMP-9 expression caused by the CS and LPS exposure, which was closely involved in suppression of Erk phosphorylation. These results suggest that MTWE possesses a potential for the treatment of COPD.