GWAS analysis reveals the genetic basis of blast resistance associated with heading date in rice.

Rice blast is a destructive fungal disease affecting rice plants at various growth stages, significantly threatening global yield stability. Development of resistant rice cultivars stands as a practical means of disease control. Generally, association mapping with a diversity panel powerfully identifies new alleles controlling trait of interest. On the other hand, utilization of a breeding panel has its advantage that can be directly applied in a breeding program. In this study, we conducted a genome-wide association study (GWAS) for blast resistance using 296 commercial rice cultivars with low population structure but large phenotypic diversity. We attempt to answer the genetic basis behind rice blast resistance among early maturing cultivars by subdividing the population based on its Heading date 1 (Hd1) functionality. Subpopulation-specific GWAS using the mixed linear model (MLM) based on blast nursery screening conducted in three years revealed a total of 26 significant signals, including three nucleotide-binding site leucine-rich repeat (NBS-LRR) genes (Os06g0286500, Os06g0286700, and Os06g0287500) located at Piz locus on chromosome 6, and one at the Pi-ta locus (Os12g0281300) on chromosome 12. Haplotype analysis revealed blast resistance associated with Piz locus was exclusively specific to Type 14 hd1 among japonica rice. Our findings provide valuable insights for breeding blast resistant rice and highlight the applicability of our elite cultivar panel to detect superior alleles associated with important agronomic traits.

Allelic combinations of Hd1, Hd16, and Ghd7 exhibit pleiotropic effects on agronomic traits in rice.

Heading date is a critical agronomic trait that significantly affects grain yield and quality in rice. As early heading is typically associated with reduced yield due to shorter growth duration, it is essential to harness optimum heading date genes and their allelic combinations to promote heading while minimizing yield penalties. In this study, we identified quantitative trait loci (QTLs) for heading date and other major agronomic traits in a recombinant inbred line (RIL) population derived from a cross between Koshihikari and Baegilmi. Analyses on 3 major QTLs for heading date and their underlying genes (Hd1, Hd16, and Ghd7) revealed their pleiotropic effects on culm length, panicle length, and head rice percentage. Additionally, Ghd7 exhibited pleiotropic effects on panicle number and grain size. Among 8 different types of allelic combinations of the 3 heading date genes, RILs carrying a single nonfunctional hd16 or ghd7 under the functional background of the other 2 genes (Hd1hd16Ghd7 and Hd1Hd16ghd7) showed potential for maintaining yield and quality-related traits while accelerating heading. These results provide valuable insights for fine-tuning heading dates in rice breeding programs.

Comparison of the analgesic effect of intrathecal morphine between laparoscopic and open living donor hepatectomy: Propensity score matching analysis.

Laparoscopic donor hepatectomy is being increasingly adopted in transplant programs due to its numerous advantages. However, the role of intrathecal morphine (ITM) in laparoscopic donor hepatectomy has not been thoroughly investigated. This study aimed to compare the analgesic effects and safety of ITM between laparoscopic and open donor hepatectomy. This retrospective study included 742 donors who underwent hepatectomy with ITM between April 2007 and June 2019. Among them, 168 and 574 donors underwent laparoscopic hepatectomy (LH) and open hepatectomy (OH), respectively. Propensity score matching yielded two comparable groups of 168 donors each. The primary endpoint was the incidence of moderate-to-severe pain (maximum numerical rating scale [NRS] pain score ≥ 4) within 24 postoperative hours. The LH group had a significantly lower incidence of moderate-to-severe pain within 24 postoperative hours than the OH group (16.1% vs 64.3%, P < .001). Moreover, the cumulative rescue intravenous opioids (in morphine-equivalent dose) on postoperative day (POD) 1 was lower in the LH group than in the OH group (3.3 [0-8.3] mg vs 10 [3.3-17.3] mg; P < .001). There were no significant between-group differences in the incidence of respiratory depression (2.4% vs 0.6%; P = .371) and prescriptions for pruritus (14.3% vs 15.5%; P = .878). However, the prescriptions for postoperative nausea and vomiting (PONV) was significantly higher in the LH group than in the OH group (64.9% vs 41.7%; P < .001). The predictors of antiemetic agent prescription included the use of laparoscopic procedure (adjusted odds ratio [OR], 2.05; 95% confidence interval [CI], 1.11-3.79; P = .021) and female sex (adjusted OR, 5.63; 95% CI, 3.19-9.92; P < .001). Preoperative ITM administration resulted in a significantly lower incidence of moderate-to-severe pain within 24 postoperative hours after laparoscopic donor hepatectomy than after open donor hepatectomy.

Quarantining: a mentally distressful but physically comfortable experience in South Korea.

OBJECTIVE: Quarantine is the first response to the COVID-19 pandemic. Restricting daily life can cause several problems. This study aimed to measure the impact of the COVID-19 quarantine on health-related quality of life (HRQoL) by comparing to the pre-pandemic. METHODS: HRQoL during COVID-19 quarantine was surveyed online using EQ-5D index and matched to that of the pre-pandemic-extracted from nationwide representative data of the Korea Community Health Survey- with propensity scores. A beta regression for the EQ-5D scores and a logistic analysis for individual dimensions of the EQ-5D index were performed to measure the impact of the COVID-19 quarantine on health utility. RESULTS: The overall scores of the EQ-5D index were significantly higher in the group under quarantine during the COVID-19 pandemic (0.971 SD 0.064) than those before the pandemic (0.964 SD 0.079, Diff. 0.007 SD 0.101, p = 0.043). The beta regression for the overall scores of EQ-5D revealed that quarantining during the COVID-19 pandemic increased by 52.7% compared to normal life before the outbreak(p = 0.045). Specifically, "Depression/Anxiety" deteriorated significantly during quarantining (OR = 0.62, 95% CI:0.48-0.80). However, "Pain/Discomfort" and "Mobility" significantly improved (OR = 5.37, 95% CI:3.71-7.78 and OR = 2.05, 95% CI:1.11-3.80, respectively). CONCLUSION: Although the world is facing a challenging moment that it has never been through before, mandatory quarantine has served as an experience that provided mental distress but physical comfort in the Korean context.

Histological characterization of anther structure in Tetep-cytoplasmic male sterility and fine mapping of restorer-of-fertility gene in rice.

Cytoplasmic male sterility (CMS) is a maternally inherited trait that inhibits plants from producing or releasing viable pollen. CMS is caused by mitochondrial-nuclear interaction, and can be rescued by introducing functional nuclear restorer-of-fertility (Rf) gene. The Tetep-CMS/Rf lines were developed through successive inter-subspecific backcrosses between indica and japonica rice accessions. Phenotypic characterization of Tetep-CMS lines revealed abnormal anther dehiscence and the inability to release, while possessing functional pollen. Transverse sections of developing anthers collected from CMS plants showed connective tissue deformities and aberrant dehydration of endothecium and epidermis. Fine mapping of Rf-Tetep using a series of segregating populations, delimited the candidate region to an approximately 109 kb genomic interval between M2099 and FM07 flanking markers. Nanopore long-read sequencing and genome assembly, proceeded by gene prediction and annotation revealed 11 open reading frames (ORFs) within the candidate region, and suggest ORF6 annotated as pentatricopeptide repeat motif containing gene 1 (PPR1), as a possible candidate gene responsible for fertility restoration. This study suggests that tissue-specific abnormalities in anthers are responsible for indehiscence-based sterility, and propose that the functional Rf gene is derived from allelic variation between inter-subspecies in rice.

What Matters for Depression and Anxiety During the COVID-19 Quarantine?: Results of an Online Cross-Sectional Survey in Seoul, South Korea.

Background: Amid the COVID-19 pandemic, quarantine measures are key to containing the spread of the virus. Millions of people have been required to quarantine throughout the pandemic; the quarantine itself is considered detrimental to mental health conditions. Objective: This study aims to investigate the factors associated with depression and anxiety among quarantined people in Seoul, South Korea. Methods: An online cross-sectional survey was administered from October to November 2020 involving people who were living in Seoul, aged 19 years or above, under a 2-week mandatory quarantine. Their mental health status was measured using the Patient Health Questionnares-9 (PHQ-9) and the General Anxiety Disorder-7 (GAD-7). Results: Overall, 1,135 respondents were finally included, resulting in a 22.0% response rate. After controlling for potential confounders, variables, such as the "second half of quarantine period" (OR = 1.78 95% CI: 1.10-2.88), "female" (OR = 1.91 95% CI: 1.16-3.16), and "having pre-existing depression" (OR = 8.03 95% CI: 2.96-21.78) were significantly associated with depression while being quarantined. Those with correct knowledge about the rationale behind for the quarantine (OR = 0.39 95% CI: 0.21-0.72), an understanding of quarantine rules (OR = 0.68 95%CI: 0.52-0.91), and those who felt supported by others (OR = 0.74 95% CI: 0.55-0.99) were less likely to develop depression while quarantining. Similarly, anxiety was significantly associated with the second week (OR = 4.18 95% CI: 1.44-12.09), those with an unstable job status (OR = 3.95 95% CI: 1.60-9.79), perceived support (OR = 0.66, 95% CI: 0.45-0.96), and the fear of being infected (OR = 7.22 95% CI: 1.04-49.95). Conclusions: This study highlights the need to develop precautionary measures to prevent depression and anxiety among people undergoing COVID-19 quarantine. In particular, individuals with depression prior to quarantine should be carefully monitored during the quarantine. Further studies with larger populations are needed.

The effect of ultrasound-guided transversus abdominis plane block on pulmonary function in patients undergoing laparoscopic cholecystectomy: a prospective randomized study.

BACKGROUND: Transversus abdominis plane block (TAPB) is commonly used for postoperative pain control after laparoscopic cholecystectomy. However, few studies have analyzed its effect on pulmonary function. The goal of this study was to elucidate the effect of ultrasound-guided bilateral TAPB on pulmonary function preservation and analgesia after laparoscopic cholecystectomy. METHODS: We enrolled 58 patients who underwent laparoscopic cholecystectomy. Among them, 53 were randomized to group T (n = 27) and group C (n = 26). Group T and group C received ultrasound-guided bilateral TAPB with 40 ml of 0.375% ropivacaine and 40 ml of 0.9% normal saline, respectively. Visual analog scale (VAS) scores, patient-controlled analgesia (PCA) consumption, forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FEV1/FVC, peak expiratory flow rate (PEF), and modified Borg scale scores were measured until 24 h post-surgery. RESULTS: The VAS scores were significantly lower in group T than in group C at 1 and 8 h after the surgery. PCA consumption was significantly lower in group T than in group C at all postoperative time points. FEV1, PEF, and FEV1/FVC were more preserved in group T than in group C at 1 h. Group T had significantly lower modified Borg scale scores than did group C at 1 and 8 h. CONCLUSION: Ultrasound-guided TAPB is effective in pulmonary function preservation and pain control after laparoscopic cholecystectomy. Therefore, it could be a great option for multimodal analgesia, preservation of pulmonary function, prevention of pulmonary complications including atelectasis, and promotion of postoperative recovery after laparoscopic cholecystectomy. CLINICAL REGISTRATION: This study was enrolled in the Clinical Research Information Service (Clinical Research Information Service, KCT0004435, Hwa Yong Shin, 2019-08-19).

Hypertrophic osteoarthropathy in renal cell carcinoma - A case report.

BACKGROUND: Hypertrophic osteoarthropathy (HOA) is a rare clinical condition including an abnormal periosteal reaction in the long bones that causes painful swelling and tenderness of the extremities, digital clubbing, arthritis, synovitis, and joint effusions. Most cases are associated with tumorous conditions and most commonly with lung cancer. HOA has been rarely reported in association with other cancers. CASE: A patient with a history of recurrent renal cell carcinoma was referred to our clinic with bilateral leg pain, knee joint effusion, and arthritis. Simple radiography and bone scintigraphy confirmed a diagnosis of HOA. Oral non-steroidal anti-inflammatory drugs, joint fluid aspiration, and intra-articular injection of pain medications were found to be effective in the management of HOA pain. CONCLUSIONS: HOA prognosis depends on the underlying disease, therefore, cancer treatment is critical. This case demonstrates the need to consider HOA in patients with various malignancies who present with bone or joint pain of the extremities.

Identification of a Candidate Gene for the Novel Cytoplasmic Male Sterility Derived from Inter-Subspecific Crosses in Rice (Oryza sativa L.).

Tetep-cytoplasmic male sterility (CMS) was developed through successive backcrosses between subspecies indica and japonica in rice (Oryza sativa L.), which showed abnormal anther dehiscence phenotypes. Whole genome sequencing and de novo assembly of the mitochondrial genome identified the chimeric gene orf312, which possesses a transmembrane domain and overlaps with two mitotype-specific sequences (MSSs) that are unique to the Tetep-CMS line. The encoded peptide of orf312 was toxic to Escherichia coli and inhibited cell growth compared to the control under isopropyl-ß-D-1-thiogalactopyranoside (IPTG) induction. The peptide of orf312 contains COX11-interaction domains, which are thought to be a main functional domain for WA352c in the wild abortive (WA-CMS) line of rice. A QTL for Rf-Tetep (restorer-of-fertility gene(s) originating from Tetep) was identified on chromosome 10. In this region, several restorer genes, Rf1a, Rf1b, and Rf4, have previously been reported. Collectively, the interactions of orf312, a candidate gene for Tetep-CMS, and Rf-Tetep, a restorer QTL, confer male sterility and fertility restoration, respectively, which enables a hybrid rice breeding system. Further studies on orf312 and isolation of Rf-Tetep will help to identify the underlying molecular mechanism of mitochondrial ORFs with the COX11-interaction domains.

Ultrasound-guided treatment of common peroneal neuropathy caused by Baker's cyst: a clinical note - A case report.

BACKGROUND: Baker's cysts are usually located in the posteromedial side of the knee and seldom cause neuropathy. CASE: We describe the rare case of a 57-year-old woman with a popliteal cyst who presented with limping gait and pain in her lower leg. She was electronically diagnosed with common peroneal neuropathy and transferred to our pain clinic. On ultrasound examination, about 2.0 × 1.2 cm sized popliteal cyst was found to extend to the fibular head, compressing the common peroneal nerve. Therefore, ultrasound-guided aspiration of the cyst and a common peroneal nerve block were performed. Immediately after the procedure, the pain, dysesthesia, and limping gait were relieved. Although her pain and dysesthesia were relieved, she underwent the surgery because of limping gait. CONCLUSIONS: In this case, we found the Baker's cyst, the cause of the common peroneal neuropathy, and treated it immediately by just simple ultrasound examination and aspiration.

Development and Validation of a Sexual-Outlook Questionnaire (SOQ) for Adult Populations in the Republic of Korea.

A Sexual Outlook Questionnaire (SOQ) that can apply to a wide range of Korean populations, including disabled people, was necessary for comprehensive research on improving clinical practice of sexual education and developing sex-related intervention programs. We developed the SOQ and tested its validity with exploratory and confirmatory factor analysis and multi-trait/-item matrix analyses. Internal consistency was assessed using Cronbach's α coefficient for item total correlations. We studied a total of 334 married or previously married adults with no cognitive impairment in the community settings. The eleven survey items were included in the final SOQ. Three factors were found: The first, "personal benefit", was devoted to the impact of one's sexual life and included four questions about the health-promoting effects and their recognition of healthiness, youth, and vitality as benefits of their sexual life. The second, "relational value", included four questions about sex as an expression of love and means of communication, and its effect on the improvement of their relationship with their spouse (partner). The third, "sexual endeavor", included three questions about the handling of sex-related problems, consulting with an expert, and sexual education. The questionnaire can briefly measure the sexual outlook of any married or previously married adult, regardless of disability.

Protective Effects of Oenothera biennis against Hydrogen Peroxide-Induced Oxidative Stress and Cell Death in Skin Keratinocytes.

BACKGROUND: Oenothera biennis (evening primrose) produces bioactive substances with a diverse range of pharmacological functions. However, it is currently unknown whether extract prepared from the aerial parts of O. biennis (APOB) can protect the skin against oxidative stress. OBJECTIVE: The aim of this study is to investigate the protective effects of APOB against oxidative stress-induced damage in human skin keratinocytes (HaCaT) and elucidate the underlying mechanisms. METHODS: We pretreated HaCaT cells with various concentrations of APOB or the antioxidant N-acetyl-L-cysteine before applying H2O2. We then compared the cell viability, intracellular reactive oxygen species (ROS) production, and DNA and mitochondrial damage between pretreated and untreated control cells using a range of assays, flow cytometry, and Western blot analysis and also examined the reducing power and DPPH free radical scavenging activity of APOB. RESULTS: APOB pretreatment significantly increased cell viability, effectively attenuated H2O2-induced comet tail formation, and inhibited H2O2-induced phosphorylation of the histone γH2AX, as well as the number of apoptotic bodies and Annexin V-positive cells. APOB was found to have high reducing power and DPPH radical scavenging activity and also exhibited scavenging activity against intracellular ROS accumulation and restored the loss of mitochondrial membrane potential caused by H2O2. APOB pretreatment almost totally reversed the enhanced cleavage of caspase-3, the degradation of poly (ADP-ribose)-polymerase (PARP), DNA fragmentation that usually occurs in the presence of H2O2, and increased the levels of heme oxygenase-1 (HO-1), a potent antioxidant enzyme that is associated with the induction of nuclear factor-erythroid 2-related factor 2 (Nrf2). CONCLUSIONS: APOB can protect HaCaT cells from H2O2-induced DNA damage and cell death by blocking cellular damage related to oxidative stress via a mechanism that affects ROS elimination and by activating the Nrf2/HO-1 signaling pathway.

Improvement of the Antioxidant Activity, Water Solubility, and Dispersion Stability of Prickly Pear Cactus Fruit Extracts Using Argon Cold Plasma Treatment.

Microwave-powered cold plasma (CP) treatment was evaluated as a means to increase the antioxidant activity, water solubility, and dispersion stability of prickly pear cactus fruit (Opuntia ficus-indica (L.) Mill.) extract. The extract (2 g) was treated at various CP generation powers and treatment times at 25 °C to 28 °C. The antioxidant activity of the prickly pear cactus fruit extract increased by 1.8% and 1.7% after CP treatment at 750 W for 40 min and 856 W for 36 min, respectively. Both the water solubility and dispersion stability (delta backscattering) of the extract increased by 2.4% and 0.1%, respectively, following CP treatment at 644 W for 36 min. These results suggest the potential of CP treatment to increase the applicability of the prickly pear cactus fruit extract and possibly other insoluble natural antioxidant compounds in foods by improving their antioxidant activities and solubility in water. PRACTICAL APPLICATION: Prickly pear cactus fruit is a functional food with a high antioxidant concentration. This study demonstrated that cold plasma treatment improved the water solubility and dispersion stability of prickly pear cactus fruit extract without altering or improving its antioxidant activity. The obtained results suggested the potential of applying cold plasma technology to improve the applicability of the extract, which is difficult to solubilize in food systems, to various processed foods.

Complete Genome Sequence of Leuconostoc kimchii Strain NKJ218, Isolated from Homemade Kimchi.

Leuconostoc kimchii strain NKJ218 was isolated from homemade kimchi in South Korea. The whole genome was sequenced using the PacBio RS II and Illumina NovoSeq 6000 platforms. Here, we report a genome sequence of strain NKJ218, which consists of a 1.9-Mbp chromosome and three plasmid contigs. A total of 2,005 coding sequences (CDS) were predicted, including 1,881 protein-coding sequences.

Dose-Dependent Neuroprotective Effect of Standardized Bee Venom Phospholipase A2 Against MPTP-Induced Parkinson's Disease in Mice.

Parkinson's disease (PD) is a chronic progressive neurodegenerative movement disorder characterized by the selective loss of dopaminergic neurons within the substantia nigra (SN). While the precise etiology of dopaminergic neuronal demise is elusive, multiple lines of evidence indicate that neuroinflammation is involved in the pathogenesis of PD. We have previously demonstrated that subcutaneous administration of bee venom (BV) phospholipase A2 (bvPLA2) suppresses dopaminergic neuronal cell death in a PD mouse model. In the present study, we established standardized methods for producing bvPLA2 agent isolated from crude BV at good manufacturing practice (GMP) facility. The therapeutic efficacy of purified bvPLA2 agent was examined in MPTP-induced PD mice. Importantly, administration of purified bvPLA2 in a dose-dependent manner reversed motor deficits in PD mice as well as inhibited loss of dopaminergic neurons within the SN of PD mice. The concentration-dependent action of standardized bvPLA2 appeared to be related to the induction of CD4+CD25+Foxp3+ regulatory T cells (Tregs), which, in part, inhibits T helper 1 (Th1) and Th17 polarization and suppresses microglial activation in PD mice. Taken together, these results suggest that standardized bvPLA2 purified from BV shows a neuroprotective effect against PD and thus has a potential target for treatment of PD.

Effects of the treatment parameters on the efficacy of the inactivation of Salmonella contaminating boiled chicken breast by in-package atmospheric cold plasma treatment.

The effects of surface coating, microbial loading, surface-to-volume ratio, sample stacking, mixing of samples with romaine lettuce, and shaking of the samples on the inactivation of Salmonella contaminating boiled chicken breast (BCB) cubes using in-package atmospheric dielectric barrier discharge cold plasma (ADCP) treatment at 38.7 kV were investigated. Whey protein coating increased the ADCP treatment efficacy in inactivating Salmonella on BCB cubes; the D-value increased from 0.2 to 1.3 min when the initial inoculum concentration increased from 3.8 to 5.7 log CFU/sample. ADCP decontaminated stacked BCB samples uniformly, and shaking during the treatment increased the inactivation rate. The concentrations of chicken protein isolate, water, and soybean oil in a chicken breast model food that resulted in the highest Salmonella reduction (1.7 log CFU/sample) were 20.5%, 68.9%, and 10.6%, respectively. ADCP treatment did not affect the color and tenderness of the model food, irrespective of its composition. The present study indicated that ADCP is a feasible technology to decontaminate prepackaged ready-to-eat meat cube products.

Protein energy malnutrition alters mucosal IgA responses and reduces mucosal vaccine efficacy in mice.

Oral vaccine responsiveness is often lower in children from less developed countries. Childhood malnutrition may be associated with poor immune response to oral vaccines. The present study was designed to investigate whether protein energy malnutrition (PEM) impairs B cell immunity and ultimately reduces oral vaccine efficacy in a mouse model. Purified isocaloric diets containing low protein (1/10 the protein of the control diet) were used to determine the effect of PEM. PEM increased both nonspecific total IgA and oral antigen-specific IgA in serum without alteration of gut permeability. However, PEM decreased oral antigen-specific IgA in feces, which is consistent with decreased expression of polymeric Immunoglobulin receptor (pIgR) in the small intestine. Of note, polymeric IgA was predominant in serum under PEM. In addition, PEM altered B cell development status in the bone marrow and increased the frequency of IgA-secreting B cells, as well as IgA secretion by long-lived plasma cells in the small intestinal lamina propria. Moreover, PEM reduced the protective efficacy of the mucosally administered cholera vaccine and recombinant attenuated Salmonella enterica serovar Typhimurium vaccine in a mouse model. Our results suggest that PEM can impair mucosal immunity where IgA plays an important role in host protection and may partly explain the reduced efficacy of oral vaccines in malnourished subjects.

Natural killer T cell sensitization during neonatal respiratory syncytial virus infection induces eosinophilic lung disease in re-infected adult mice.

Respiratory syncytial virus (RSV) is a major viral pathogen that causes severe lower respiratory tract infections in infants and the elderly worldwide. Infants with severe RSV bronchiolitis tend to experience more wheezing and asthma in later childhood. Because invariant natural killer T (iNKT) cells are associated with the asthma pathology, we investigated whether neonatal iNKT cells are involved in the aggravation of pulmonary diseases following RSV infection in mice. Intranasal exposure to the iNKT cell ligand α-galactosylceramide (α-GC) with RSV primary infection in neonatal mice elicited neither cytokine production (except for a slight increase of IL-5) nor pulmonary eosinophilia, despite the presence of both CD1d+ cells and NKT cells. Interestingly, in adult mice re-infected with RSV, neonatal iNKT cell sensitization by α-GC during RSV primary infection resulted in much higher levels of pulmonary Th2 cytokines and elevated eosinophilia with airway hyperresponsiveness, whereas this was not observed in cd1d knockout mice. In contrast, α-GC priming of adults during RSV re-infection did not induce more severe airway symptoms than RSV re-infection in the absence of α-GC. α-GC co-administration during RSV primary infection facilitated RSV clearance regardless of age, but viral clearance following re-infection was not iNKT cell-dependent. This study clearly demonstrates that RSV-induced immune responses can be altered by iNKT cells, suggesting that neonatal iNKT cell sensitization during RSV primary infection is associated with exacerbation of pulmonary diseases following RSV re-infection in adulthood.

Bee Venom Phospholipase A2 Ameliorates House Dust Mite Extract Induced Atopic Dermatitis Like Skin Lesions in Mice.

Atopic dermatitis (AD) is a biphasic inflammatory skin disease that is provoked by epidermal barrier defects, immune dysregulation, and increased skin infections. Previously, we have demonstrated that bvPLA2 evoked immune tolerance by inducing regulatory T cells (Treg), and thus alleviated Th2 dominant allergic asthma in mice. Here, we would like to determine whether treatment with bvPLA2 exacerbates the AD-like allergic inflammations induced by house dust mite extract (DFE) in a murine model. Epidermal thickness, immune cell infiltration, serum immunoglobulin, and cytokines were measured. Ear swelling, skin lesions, and the levels of total serum IgE and Th1/Th2 cytokines were elevated in DFE/DNCB-induced AD mice. Topical application of bvPLA2 elicited significant suppression of the increased AD symptoms, including ear thickness, serum IgE concentration, inflammatory cytokines, and histological changes. Furthermore, bvPLA2 treatment inhibited mast cell infiltration into the ear. On the other hand, Treg cell depletion abolished the anti-atopic effects of bvPLA2, suggesting that the effects of bvPLA2 depend on the existence of Tregs. Taken together, the results revealed that topical exposure to bvPLA2 aggravated atopic skin inflammation, suggesting that bvPLA2 might be a candidate for the treatment of AD.

Rosmarinic Acid Methyl Ester Inhibits LPS-Induced NO Production via Suppression of MyD88- Dependent and -Independent Pathways and Induction of HO-1 in RAW 264.7 Cells.

In this study, we investigated the anti-inflammatory effect of rosmarinic acid methyl ester (RAME) isolated from a mutant cultivar of Perilla frutescens (L.) Britton. We found that RAME inhibits lipopolysaccharide (LPS)-induced nitric oxide (NO) production, with an IC50 of 14.25 µM, in RAW 264.7 cells. RAME inhibited the LPS-induced expression of pro-inflammatory cytokines including interleukin (IL)-1ß, IL-6, IL-10, monocyte chemoattractant protein-1, interferon-ß, and inducible nitric oxide synthase (iNOS). Moreover, RAME suppressed the activation of nuclear factor kappa B. These results suggest that the downregulation of iNOS expression by RAME was due to myeloid differentiation primary response gene 88 (MyD88)-dependent and -independent pathways. Furthermore, RAME induced the expression of heme oxygenase-1 (HO-1) through activation of nuclear factor-erythroid 2-related factor 2. Treatment with tin protoporphyrin, an inhibitor of HO-1, reversed the RAME-induced suppression of NO production. Taken together, RAME isolated from P. frutescens inhibited NO production in LPS-treated RAW 264.7 cells through simultaneous induction of HO-1 and inhibition of MyD88-dependent and -independent pathways.