Neuroprotective Effect of Macrophage Migration Inhibitory Factor (MIF) in a Mouse Model of Ischemic Stroke.

The mechanism of the neuroprotective effect of the macrophage migration inhibitory factor (MIF) in vivo is unclear. We investigated whether the MIF promotes neurological recovery in an in vivo mouse model of ischemic stroke. Transient middle cerebral artery occlusion (MCAO) surgery was performed to make ischemic stroke mouse model. Male mice were allocated to a sham vehicle, a sham MIF, a middle cerebral artery occlusion (MCAO) vehicle, and MCAO+MIF groups. Transient MCAO (tMCAO) was performed in the MCAO groups, and the vehicle and the MIF were administered via the intracerebroventricular route. We evaluated the neurological functional scale, the rotarod test, and T2-weighted magnetic resonance imaging. The expression level of the microtubule-associated protein 2 (MAP2), Bcl2, and the brain-derived neurotrophic factor (BDNF) were further measured by Western blot assay. The Garcia test was significantly higher in the MCAO+MIF group than in the MCAO+vehicle group. The MCAO+MIF group exhibited significantly better performance on the rotarod test than the MCAO+vehicle group, which further had a significantly reduced total infarct volume on T2-weighted MRI imaging than the MCAO vehicle group. Expression levels of BDNF, and MAP2 tended to be higher in the MCAO+MIF group than in the MCAO+vehicle group. The MIF exerts a neuroprotective effect in an in vivo ischemic stroke model. The MIF facilitates neurological recovery and protects brain tissue from ischemic injury, indicating a possibility of future novel therapeutic agents for stroke patients.

Survey of characteristics of exposure to mainstream cigarette smoke using discarded cigarette butts from Korean smokers.

Evaluating the characteristics of exposure to mainstream cigarette smoke is an essential field in tobacco research because of the large risk burden among smokers. Detailed evaluation of the complex factors pertaining to the exposure of smokers to mainstream cigarette smoke was attempted by analysis of discarded cigarette butts. A total of 5475 samples of discarded cigarette butts was collected to investigate the exposure characteristics in relation to Korean smokers. The basic physico-chemical characteristics of cigarettes, including the filter length, filter type, menthol addition, and nicotine and tar content, were determined and the manufacturer and cigarette size were identified. The tobacco-burned percentage (TBP)) and tar staining were used as physical markers, and actual human exposure to cigarette smoke was determined using the part filter method. Multiple linear regression analyses and generalized ordinal logistic regression analysis were conducted to identify the relationship between the socio-demographic factors and the physico-chemical characteristics of the cigarettes themselves and the exposure characteristics. Significant associations were observed between the TBP and age group, occupational group, manufacturer, tar staining, ISO tar content, and filter length. Increased odds of smoking with a heavier tar stain among Korean smokers were associated with blue collar workers vs. other workers, manufacturer B vs. other manufacturers, recess filter vs. other filter types, ISO tar content, and TBP. Finally, significant associations between the log-transformed human-smoked tar and nicotine yields and occupational group, the TBP, tar staining, and physico-chemical properties of cigarettes were found and were used to propose models for predicting the actual exposure to tar and nicotine. The proposed models account for 60-61% and 47-49% of the variance of human exposure to tar and nicotine, respectively. This analysis of discarded cigarette butts revealed that various factors, including socio-demographic factors such as age group and occupational group, as well as the physico-chemical properties of cigarette products such as the filter type and length, cigarette size, ISO tar and nicotine content, and mentholation, affect the characteristics of exposure of Korean smokers to mainstream cigarette smoke.

Sex-biased gene expression in antennae of Drosophila suzukii.

Drosophila suzukii differs from other members of the genus Drosophila in its host preference and oviposition behavior. The flies are attracted to ripening fruits, and females have a serrated ovipositor enabling eggs to be laid inside the fruit. In addition to its huge economic impact, its unique chemoecological, morphological, and physiological characteristics have garnered considerable research interests. In this study, we analyzed D. suzukii antennal transcriptomes to identify sex-biased genes by comparison of differential gene expressions between male antennae (MA) and female antennae (FA). Among 13,583 total genes of the fly genome, 11,787 genes were expressed in either MA or FA. There are only 132 genes (9 in MA, 7 in FA, and 116 in both, FPKM >1) were expressed in antennae exclusively, and 2,570 genes (9 in MA, 0 in FA, and 2,561 in both) were enriched in antennae containing 185 and 113 sex-biased genes in MA and FA, respectively. Interestingly, many immune-related genes were highly expressed in MA, whereas several chemosensory genes were at high rank in FA. We identified 27 sex-biased chemosensory genes including odorant and gustatory receptors, odorant-binding proteins, chemosensory proteins, ionotropic receptors, and cytochrome P450s, and validated the gene expressions using quantitative real-time PCR. The highly expressed sex-biased genes in antennae are likely involved in the fly specific mating, host-finding behaviors, or sex-specific functions. The molecular results demonstrated here will facilitate to find the unique chemoreception of D. suzukii, as well as on the development of new management strategies for this pest.

Antiadipogenic Effects of Mixtures of Cornus officinalis and Ribes fasciculatum Extracts on 3T3-L1 Preadipocytes and High-Fat Diet-Induced Mice.

Medicinal plants have been used worldwide as primary alternative healthcare supplements. Cornus officinalis (CO) and Ribes fasciculatum (RF) are traditional medicinal plants applied in East Asia to treat human diseases such as hepatitis, osteoporosis, oxidative stress and allergy. The aim of this study was to examine the anti-obesity effect of CO and RF on preadipocyte 3T3-L1 cells in vitro and high-fat diet (HFD)-induced obesity mice in vivo. Combination treatment of CO and RF in differentiated 3T3-L1 cells inhibited adipocyte differentiation through downregulation of adipogenesis-associated genes such as CCAAT/enhancer-binding protein alpha (Cebpa), fatty acid binding protein 4 (Fabp4), peroxisome proliferator-activated receptor gamma (Pparg) and sterol regulatory element binding protein (Srebp1). In vivo animal models showed that a mixture of CO and RF inhibited HFD-induced weight gain, resulting in decreased abdominal visceral fat tissues and fatty hepatocyte deposition. In addition, CO+RF treatment decreased HFD-induced adipogenesis-associated genes in abdominal white fat tissue. These results suggest that administration of a CO and RF mixture prevented adipocyte differentiation and lipid accumulation in preadipocyte cells and HFD-induced body weight in obesity mice. Therefore, combined therapy of CO and RF may be a protective therapeutic agent against obesity.

Antiobesity Effects of Gentiana lutea Extract on 3T3-L1 Preadipocytes and a High-Fat Diet-Induced Mouse Model.

Obesity is one of the most common metabolic diseases resulting in metabolic syndrome. In this study, we investigated the antiobesity effect of Gentiana lutea L. (GL) extract on 3T3-L1 preadipocytes and a high-fat-diet (HFD)-induced mouse model. For the induction of preadipocytes into adipocytes, 3T3-L1 cells were induced by treatment with 0.5 mM 3-isobutyl-1-methylxanthine, 1 mM dexamethasone, and 1 µg/mL insulin. Adipogenesis was assessed based on the messenger ribonucleic acid expression of adipogenic-inducing genes (adiponectin (Adipoq), CCAAT/enhancer-binding protein alpha (Cebpa), and glucose transporter type 4 (Slc2a4)) and lipid accumulation in the differentiated adipocytes was visualized by Oil Red O staining. In vivo, obese mice were induced with HFD and coadministered with 100 or 200 mg/kg/day of GL extract for 12 weeks. GL extract treatment inhibited adipocyte differentiation by downregulating the expression of adipogenic-related genes in 3T3-L1 cells. In the obese mouse model, GL extract prevented HFD-induced weight gain, fatty hepatocyte deposition, and adipocyte size by decreasing the secretion of leptin and insulin. In conclusion, GL extract shows antiobesity effects in vitro and in vivo, suggesting that this extract can be beneficial in the prevention of obesity.

SIRT2 reduces actin polymerization and cell migration through deacetylation and degradation of HSP90.

SIRT2, a member of the class III histone deacetylase family, has been identified as a tumor suppressor, which is associated with various cellular processes including metabolism and proliferation. However, the effects of SIRT2 on cancer cell migration caused by cytoskeletal rearrangement remain uncertain. Here we show that SIRT2 inhibits cell motility by suppressing actin polymerization. SIRT2 regulates actin dynamics through HSP90 destabilization and subsequent repression of LIM kinase (LIMK) 1/cofilin pathway. SIRT2 directly interacts with HSP90 and regulates its acetylation and ubiquitination. In addition, the deacetylase activity of SIRT2 is required for the regulation of actin polymerization and the ubiquitin-mediated proteasomal degradation of HSP90 induced by SIRT2.

Species-Specific Interactions between Plant Metabolites and Insect Juvenile Hormone Receptors.

Because juvenile hormone (JH) controls insect development and its analogs are used as insecticides, juvenile hormone disruptors (JHDs) represent potential sources from which novel pesticides can be developed. Many plant species harbor JHD activity, which has previously been attributed plant secondary metabolites (i.e., diterpenes) that disrupt insect development by interfering with the JH-mediated heterodimer formation of insect juvenile receptor complexes. The results of the present study indicate that plant JHD activity is also concentrated in certain plant groups and families and that plant metabolites have insect group-specific activity. These findings suggest that reciprocal diversification has occurred between plants and insects through the evolution of the plant metabolites and JH receptors, respectively, and that plant metabolites could be developed into insect group-specific pesticides with limited effects on non-target species.

Diagnostic Usefulness of Varicella-Zoster Virus Real-Time Polymerase Chain Reaction Analysis of DNA in Saliva and Plasma Specimens From Patients With Herpes Zoster.

Background: We evaluated the diagnostic usefulness of polymerase chain reaction (PCR) analysis for detecting varicella-zoster virus (VZV) infection and reactivation of VZV, using DNA extracted from saliva and plasma specimens obtained from subjects with suspected herpes zoster and from healthy volunteers during stressful and nonstressful conditions. Methods: There were 52 patients with a diagnosis of herpes zoster (group 1), 30 with a diagnosis of zoster-mimicking disease (group 2), and 27 healthy volunteers (group 3). Saliva and plasma samples were evaluated for VZV DNA by real-time PCR analysis. Results: Among patients with suspected herpes zoster (ie, patients in groups 1 and 2), the sensitivity of PCR analysis of salivary DNA for detecting VZV (88%; 95% confidence interval [CI], 74%-95%) was significantly higher than that of PCR analysis of plasma DNA (28%; 95% CI, 16%-44%; P < .001), whereas the specificity of PCR analysis of salivary DNA (100%; 95% CI, 88%-100%) was similar to that of PCR analysis of plasma DNA (100%; 95% CI, 78%-100%; P > .99). VZV DNA was not detected in saliva and plasma samples from group 3 (0%; 95% CI, 0%-14%). Conclusions: Real-time PCR analysis of salivary DNA is more sensitive than that of plasma DNA for detecting VZV among patients with suspected herpes zoster. We found no subclinical reactivation of VZV in group 3 following exposure to common stressful conditions.

Conifer Diterpene Resin Acids Disrupt Juvenile Hormone-Mediated Endocrine Regulation in the Indian Meal Moth Plodia interpunctella.

Diterpene resin acids (DRAs) are important components of oleoresin and greatly contribute to the defense strategies of conifers against herbivorous insects. In the present study, we determined that DRAs function as insect juvenile hormone (JH) antagonists that interfere with the juvenile hormone-mediated binding of the JH receptor Methoprene-tolerant (Met) and steroid receptor coactivator (SRC). Using a yeast two-hybrid system transformed with Met and SRC from the Indian meal moth Plodia interpunctella, we tested the interfering activity of 3704 plant extracts against JH III-mediated Met-SRC binding. Plant extracts from conifers, especially members of the Pinaceae, exhibited strong interfering activity, and four active interfering DRAs (7α-dehydroabietic acid, 7-oxodehydroabietic acid, dehydroabietic acid, and sandaracopimaric acid) were isolated from roots of the Japanese pine Pinus densiflora. The four isolated DRAs, along with abietic acid, disrupted the juvenile hormone-mediated binding of P. interpunctella Met and SRC, although only 7-oxodehydroabietic acid disrupted larval development. These results demonstrate that DRAs may play a defensive role against herbivorous insects via insect endocrine-disrupting activity.

The herbal-derived honokiol and magnolol enhances immune response to infection with methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA).

The emergence of antibiotic resistant strains such as methicillin-resistant Staphylococcus aureus (MRSA) reminds us an urgent need to develop a new immune-modulating agent for preventing S. aureus infection. In this study, we found that herbal medicines, honokiol and magnolol, caused a significant cellular immune modulatory effect during S. aureus infection. In mouse macrophages, these compounds drove upregulation of an antioxidant effect in response to S. aureus, resulting in a dampened total cellular reactive oxygen species (ROS) production and decreased production of inflammatory cytokines/chemokines, whereas honokiol induced increased types I and III interferon messenger RNA (mRNA) expression levels in response to MSSA infection. Moreover, the internalization of S. aureus by human alveolar epithelial cells was inhibited by these compounds. Furthermore, honokiol and magnolol treatment promoted a delay in killing during MSSA infection in Caenorhabditis elegans, suggesting antimicrobial function in vivo. In conclusion, honokiol and magnolol may be considered as attractive immune-modulating treatment for S. aureus infection.

In vitro and in vivo antimicrobial efficacy of natural plant-derived compounds against Vibrio cholerae of O1 El Tor Inaba serotype.

In this study, we investigated antibacterial activities of 20 plant-derived natural compounds against Gram-negative enteric pathogens. We found that both flavonoids and non-flavonoids, including honokiol and magnolol, possess specific antibacterial activities against V. cholerae, but not against other species of Gram-negative bacterium which we tested. Using various antibacterial assays, we determined that there was a dose-dependent bactericidal and biofilm inhibitory activity of honokiol and magnolol against Vibrio cholerae. In addition to antibacterial activities, these molecules also induced an attenuating effect on reactive oxygen species (ROS) production and pro-inflammatory responses generated by macrophages in response to lipopolysaccharides (LPS). Additionally, Caenorhabditis elegans lethality assay revealed that honokiol and magnolol have an ability to extend a lifespan of V. cholerae-infected worms, contributing to prolonged survival of worms after lethal infection. Altogether, our data show for the first time that honokiol and magnolol may be considered as attractive protective or preventive food adjuncts for cholera.

Luteimicrobium xylanilyticum sp. nov., isolated from the gut of a long-horned beetle, Massicus raddei.

A novel strain, designated W-15(T), was isolated from the gut of a long-horned beetle, Massicus raddei, collected in South Korea. Phylogenetic analysis based on 16S rRNA gene sequences revealed that the strains belonged to the suborder Micrococcineae. Strain W-15(T) was most closely related to Luteimicrobium album RI148-Li105(T) (97.9 % similarity). Strain W-15(T) was Gram-stain-positive, rod- and coccus-shaped and non-motile. Growth was observed at 15-37 °C, at pH 4.5-8.5 and in the presence of 0-5.0 % NaCl. The cell-wall peptidoglycan of the strain was A4α (l-Lys-d-Ser-d-Asp). The major menaquinone present in this strain was MK-8 (H2) and the major cellular fatty acids were anteiso-C15 : 0, iso-C16 : 0, iso-C15 : 0 and anteiso-C17 : 0. The major polar lipids were diphosphatidylglycerol, phosphatidylinositol, an unknown lipid, an unknown phospholipid and an unknown phosphoglycolipid. The G+C content of genomic DNA of the strain was 73.8 mol%. On the basis of evidence from our polyphasic taxonomic study, strain W-15(T) is classified as representing a novel species in the suborder Micrococcineae, for which the name Luteimicrobium xylanilyticum sp. nov. is proposed. The type strain of this species is strain W-15(T) ( = KCTC 19882(T) = JCM 18090(T)).

The effect of training using an upper limb rehabilitation robot (HEXO-UR30A) in chronic stroke patients: A randomized controlled trial.

BACKGROUND: Upper limb robotic rehabilitation can be beneficial to the patients when applied appropriately. HEXO-UR30A is a novel exoskeletal type upper limb rehabilitation robot that provides continuous passive motion to the shoulder joint. OBJECTIVE: The purpose of this study is to evaluate the effectiveness of HEXO-UR30A on the patient's functional change, spasticity, and range of motion (ROM). METHODS: We included stroke patients with upper limb hemiparesis of age > 19 years with spasticity grading of modified Ashworth scale < 3 and Brunnstrom recovery stage ≥ 4. The efficacy of the robot was investigated based on a rehabilitation program for 3 weeks. Patient's functions were compared before vs after treatment and between the HEXO group vs control. We conducted the Fugl-Meyer Assessment of the Upper Extremity, modified Barthel index, modified Ashworth scale, ROM, and Motricity Index upper limb. Patients' satisfaction was evaluated using a questionnaire after every 10 sessions of training. RESULTS: In the HEXO group, the Fugl-Meyer assessment for shoulder improved significantly (P value = .006*) compared with the control group (P value = .075). Both groups showed significant improvement (P value < .05) in Motricity Index upper limb after treatment. There were some improvements in the passive and active ROM. Patients in the HEXO group reported high satisfaction with upper limb rehabilitation. CONCLUSION: These results show that HEXO-UR30A can improve functional ability in chronic stroke patients. Moreover, the high satisfaction in patients might promote active involvement in upper limb rehabilitation.

Hepatitis B virus X protein promotes epithelial-mesenchymal transition of hepatocellular carcinoma cells by regulating SOCS1.

Hepatocellular carcinoma (HCC), a primary type of liver cancer, is one of the leading causes of cancer related deaths worldwide. HCC patients have poor prognosis due to intrahepatic and extrahepatic metastasis. Hepatitis B virus (HBV) infection is one of the major causes of various liver diseases including HCC. Among HBV gene products, HBV X protein (HBx) plays an important role in the development and metastasis of HCC. However, the mechanism of HCC metastasis induced by HBx has not been elucidated yet. In this study, for the first time, we report that HBx interacts with the suppressor of cytokine signaling 1 (SOCS1) which negatively controls NF-κB by degrading p65, a subunit of NF-κB. NF-κB activates the transcription of factors associated with epithelial-mesenchymal transition (EMT), a crucial cellular process associated with invasiveness and migration of cancer cells. Here, we report that HBx physically binds to SOCS1, subsequently prevents the ubiquitination of p65, activates the transcription of EMT transcription factors and enhance cell migration and invasiveness, suggesting a new mechanism of HBV-associated HCC metastasis. [BMB Reports 2022; 55(5): 220-225].

Inducible Expression of Several Drosophila melanogaster Genes Encoding Juvenile Hormone Binding Proteins by a Plant Diterpene Secondary Metabolite, Methyl Lucidone.

Juvenile hormones prevent molting and metamorphosis in the juvenile stages of insects. There are multiple genes encoding a conserved juvenile hormone binding protein (JHBP) domain in a single insect species. Although some JHBPs have been reported to serve as carriers to release hormones to target tissues, the molecular functions of the other members of the diverse JHBP family of proteins remain unclear. We characterized 16 JHBP genes with conserved JHBP domains in Drosophila melanogaster. Among them, seven JHBP genes were induced by feeding the flies with methyl lucidone, a plant diterpene secondary metabolite (PDSM). Induction was also observed upon feeding the juvenile hormone (JH) analog methoprene. Considering that methyl lucidone and methoprene perform opposite functions in JH-mediated regulation, specifically the heterodimeric binding between a JH receptor (JHR) and steroid receptor coactivator (SRC), the induction of these seven JHBP genes is independent of JH-mediated regulation by the JHR/SRC heterodimer. Tissue-specific gene expression profiling through the FlyAtlas 2 database indicated that some JHBP genes are mainly enriched in insect guts and rectal pads, indicating their possible role during food uptake. Hence, we propose that JHBPs are induced by PDSMs and respond to toxic plant molecules ingested during feeding.

Determining the Optimal Administration Conditions under Which MIF Exerts Neuroprotective Effects by Inducing BDNF Expression and Inhibiting Apoptosis in an In Vitro Stroke Model.

Macrophage migration inhibitory factor (MIF) exerts neuroprotective effects against cerebral ischemia/reperfusion injury by inhibiting neuronal apoptosis and inducing the expression of brain-derived neurotrophic factor (BDNF). However, the optimal administration conditions of MIF are currently unknown. Here, we aimed to identify these conditions in an in vitro model. To determine the optimal concentration of MIF, human neuroblastoma cells were assigned to one of seven groups: control, oxygen and glucose deprivation/reperfusion (OGD/R), and OGD/R with different concentrations (1, 10, 30, 60, and 100 ng/mL) of MIF. Six groups were studied to investigate the optimal administration time: control, OGD/R, and OGD/R with MIF administered at different times (pre-OGD, OGD-treat, post-OGD, and whole-processing). Water-soluble tetrazolium salt-1 assay, Western blot analysis, and immunocytochemistry were used to analyze cell viability and protein expression. We found that 60 ng/mL was the optimal concentration of MIF. However, the effects of administration time were not significant; MIF elicited similar neuroprotective effects regardless of administration time. These findings correlated with the expression of BDNF and apoptosis-related proteins. This study provides detailed information on MIF administration, which offers a foundation for future in vivo studies and translation into novel therapeutic strategies for ischemic stroke.

Zika Virus Induces Tumor Necrosis Factor-Related Apoptosis Inducing Ligand (TRAIL)-Mediated Apoptosis in Human Neural Progenitor Cells.

Zika virus (ZIKV) remains as a public health threat due to the congenital birth defects the virus causes following infection of pregnant women. Congenital microcephaly is among the neurodevelopmental disorders the virus can cause in newborns, and this defect has been associated with ZIKV-mediated cytopathic effects in human neural progenitor cells (hNPCs). In this study, we investigated the cellular changes that occur in hNPCs in response to ZIKV (African and Asian lineages)-induced cytopathic effects. Transmission electron microscopy showed the progress of cell death as well as the formation of numerous vacuoles in the cytoplasm of ZIKV-infected hNPCs. Infection with both African and Asian lineages of ZIKV induced apoptosis, as demonstrated by the increased activation of caspase 3/7, 8, and 9. Increased levels of proinflammatory cytokines and chemokines (IL-6, IL-8, IL-1ß) were also detected in ZIKV-infected hNPCs, while z-VAD-fmk-induced inhibition of cell death suppressed ZIKV-mediated cytokine production in a dose-dependent manner. ZIKV-infected hNPCs also displayed significantly elevated gene expression levels of the pro-apoptotic Bcl2-mediated family, in particular, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Furthermore, TRAIL signaling led to augmented ZIKV-mediated cell death and the knockdown of TRAIL-mediated signaling adaptor, FADD, resulted in enhanced ZIKV replication. In conclusion, our findings provide cellular insights into the cytopathic effects induced by ZIKV infection of hNPCs.

Anti-Osteoporotic Effects of the Herbal Mixture of Cornus officinalis and Achyranthes japonica In Vitro and In Vivo.

Osteoporosis is a porous bone disease caused by bone density loss, which increases the risk of fractures. Cornus officinalis (CO) and Achyranthes japonica (AJ) have been used as traditional herbal medicine for various disorders in East Asia. Although the anti-osteoporotic effects of single extract of CO and AJ have already been reported, the synergistic effect of a combined mixture has not been studied. In this study, we investigated the effects of a CO and AJ herbal mixture on osteoporosis in in vitro and in vivo models. The results demonstrate that treatment with the CO and AJ mixture significantly promoted osteoblast differentiation of MC3T3-E1 mouse preosteoblasts through the upregulation of osteoblastic differentiation-associated genes such as alkaline phosphatase (Alpl), runt-related transcription factor 2 (Runx2), and bone gamma-carboxyglutamic acid-containing protein (Bglap), while the mixture significantly inhibited differentiation of osteoclasts isolated from primary-cultured mouse monocytes. In addition, oral administration of CO and AJ mixture significantly prevented bone mineral density loss and trabecular bone structures in an ovariectomy-induced osteoporotic mouse model. These results suggest that the combination treatment of CO and AJ mixture might be a beneficial therapy for osteoporosis.

Altered Mitochondrial Functions and Morphologies in Epithelial Cells Are Associated With Pathogenesis of Chronic Rhinosinusitis With Nasal Polyps.

PURPOSE: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a complex inflammatory disease of the nasal and paranasal sinus mucosa. The disease is associated with mitochondrial dysfunction, structural changes in the mitochondria, and reactive oxygen species (ROS) generation. This study investigated whether there are functional and morphological changes in the mitochondria in the epithelial cells of nasal polyps (NPs) and Staphylococcus aureus enterotoxin B (SEB)-stimulated nasal epithelial cells. METHODS: In all, 30 patients with CRSwNP and 15 healthy subjects were enrolled. Mitochondrial ROS (mtROS) and changes in mitochondrial functions and structures were investigated in the uncinate tissue (UT) of healthy controls, the UT or NPs of CRSwNP patients, and human nasal epithelial cells with or without SEB stimulation. RESULTS: Oxidative phosphorylation complexes showed various responses following SEB stimulation in the nasal epithelial cells, and their expressions were significantly higher in the NPs of patients with CRSwNP than in the UT of controls. Generation of mtROS was increased following SEB exposure in nasal epithelial cells and was reduced by pretreatment with MitoTEMPO, which is used as an mtROS scavenger. In the tissues, mtROS was significantly increased in the NPs of CRSwNP patients compared to the UT of controls or CRSwNP patients. The expressions of fusion- and fission-related molecules were also significantly higher in SEB-exposed nasal epithelial cells than in non-exposed cells. In tissues, the expression of fission (fission mediator protein 1)- and fusion (membrane and mitofusin-1, and optic atrophy protein 1)-related molecules was significantly higher in the NPs of CRSwNP patients than in UT of controls or CRSwNP patients. Transmission electron microscopy revealed elongated mitochondria in SEB-exposed nasal epithelial cells and epithelial cells of NPs. CONCLUSIONS: Production of mtROS, disrupted mitochondrial function, and structural changes in nasal epithelial cells might be involved in the pathogenesis of CRSwNP.

Dietary exposure and risk assessment of mercury from the Korean total diet study.

As a national project, obtaining information on the amount of heavy metal exposure of individuals through food intake is an important basic parameter for risk assessment. This study was conducted to evaluate dietary exposure levels and various risks from mercury (Hg) in Korean foods. In total, 342 samples comprising 114 food items were collected and then cooked prior to analysis. As found by Hg analysis, the mean content of metal in the fish and shellfish group was highest among the 15 Korean food groups. The total daily amount of Hg intake from typical Korean foods was 2.40 microg/person/d. The daily amount (microg/person/d) of Hg intake from each food group was 0.155 in grains and cereals, 0.008 potatoes and starch, 0.005 sugars and sweets, 0.0093 pulses, 0.0018 nuts and seeds, 0.203 vegetables, 0.027 fruits, 0.021 meats and poultry, 0.004 eggs, 1.826 fish and shellfish, 0.022 seaweed, 0.043 milk and dairy products, 0.008 oils and fats, 0.042 beverages, and 0.023 seasonings. The fish and shellfish group contributed most to total dietary intake at 76%. For risk assessment, probable daily intake (PDI) was calculated and compared with provisional tolerable weekly intake (PTWI) of the Joint FAO/WHO Expert Committee on Food Additives (JECFA). The level of Hg intake through fish and shellfish of 0.001 mg/kg body weight bw/wk corresponded to 4.54% of the PTWI value of 0.005 mg/kg bw/wk, the safety standard for JECFA. The level of Hg intake through selected foods from the Food list for Koreans was 0.001 mg/kg bw/wk, corresponding to 5.95% of PTWI value. Therefore, overall intake was at levels below the recommended JECFA levels. The relative gender Hg hazard from Korean foods was 6.26% and 5.5% for males and females, respectively. The relative age Hg hazard from Korean foods was, 8.9% in those 3-6 yr old, 6.7% in those 7-12 yr old, 5.2% in those 13-19 yr old, 5.9% in those 20-29 yr old, 6.3% in those 30-49 yr old, 5.6% in those ages 50-64 yr, and 3.7% in the group of those over 65 yr of age. Relative regional Hg hazard from Korean foods was 6.3% in urban versus 5.5% in rural areas. Thus, the amount of Hg intake through consumption of Korean foods was found to be at a relatively safe level. These data may be thus used to establish safety standards for fish and shellfish consumption.