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Allergic asthma, a type of chronic airway inflammation, is a global health concern because of its increasing incidence and recurrence rates. Camellia sinensis L. yields a variety type of teas, which are also used as medicinal plants in East Asia and are known to have antioxidant, anti-inflammatory, and immune-potentiating properties. Here, we examined the constituents of C. sinensis L. extract (CSE) and evaluated the protective effects of CSE on allergic asthma by elucidating the underlying mechanism. To induce allergic asthma, we injected the sensitization solution (mixture of ovalbumin (OVA) and aluminum hydroxide) into mice intraperitoneally on days 0 and 14. Then, the mice were exposed to 1% OVA by a nebulizer on days 21 to 23, while intragastric administration of CSE (30 and 100 mg/kg) was performed each day on days 18 to 23. We detected five compounds in CSE, including (-)-epigallocatechin, caffeine, (-)-epicatechin, (-)-epigallocatechin gallate, and (-)-epicatechin gallate. Treatment with CSE remarkably decreased the airway hyperresponsiveness, OVA-specific immunoglobulin E level, and inflammatory cell and cytokine levels of mice, with a decrease in inflammatory cell infiltration and mucus production in lung tissue. Treatment with CSE also decreased the phosphorylation of nuclear factor-κB (NF-κB) and the expression of matrix-metalloproteinase (MMP)-9 in asthmatic mice. Our results demonstrated that CSE reduced allergic airway inflammation caused by OVA through inhibition of phosphorylated NF-κB and MMP-9 expression.

Abstract Background Although copper oxide nanoparticles (CuONPs) offer certain benefits to humans, they can be toxic to organs and exacerbate underlying diseases upon exposure. Chronic obstructive pulmonary disease (COPD), induced by smoking, can worsen with exposure to various harmful particles. However, the specific impact of CuONPs on COPD and the underlying mechanisms remain unknown. In this study, we investigated the toxic effects of CuONPs on the respiratory tract, the pathophysiology of CuONPs exposure-induced COPD, and the mechanism of CuONPs toxicity, focusing on thioredoxin-interacting protein (TXNIP) signaling using a cigarette smoke condensate (CSC)-induced COPD model. Results In the toxicity study, CuONPs exposure induced an inflammatory response in the respiratory tract, including inflammatory cell infiltration, cytokine production, and mucus secretion, which were accompanied by increased TXNIP, NOD-like receptor protein 3 (NLRP3), caspase-1, and interleukin (IL)-1β. In the COPD model, CuONPs exposure induced the elevation of various indexes related to COPD, as well as increased TXNIP expression. Additionally, TNXIP-knockout (KO) mice showed a significantly decreased expression of NLRP3, caspase-1, and IL-1β and inflammatory responses in CuONPs-exposed COPD mice. These results were consistent with the results of an in vitro experiment using H292 cells. By contrast, TNXIP-overexpressed mice had a markedly increased expression of NLRP3, caspase-1, and IL-1β and inflammatory responses in CuONPs-exposed COPD mice. Conclusions We elucidated the exacerbating effect of CuONPs exposure on the respiratory tract with underlying COPD, as well as related signaling transduction via TXNIP regulation. CuONPs exposure significantly increased inflammatory responses in the respiratory tract, which was correlated with elevated TXNIP-NLRP3 signaling.

Asian sand dust (ASD), a seasonal dust storm originating from the deserts of China and Mongolia, affects Korea and Japan during the spring, carrying soil particles and a variety of biochemical components. Exposure to ASD has been associated with the onset and exacerbation of respiratory disorders, although the underlying mechanisms remain unclear. This study investigates ASD-induced pulmonary toxicity and its mechanistic pathways, focusing on the role of thioredoxin-interacting protein (TXNIP). Using TXNIP knock-out (KO) mice and adeno-associated virus (AAV)-mediated TXNIP overexpression transgenic mice, we explored how TXNIP modulates ASD-induced pulmonary inflammation. Mice were exposed to ASD via intranasal administration on days 1, 3, and 5 to induce inflammation. ASD exposure led to significant pulmonary inflammation, evidenced by increased inflammatory cell counts and elevated cytokine levels in bronchoalveolar lavage fluid, as well as heightened protein expression of the TXNIP/NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome. TXNIP KO mice exhibited attenuated airway inflammation and downregulation of the NLRP3 inflammasome compared to wild-type controls, while AAV-mediated TXNIP overexpression mice showed exacerbated inflammatory responses, including elevated NLRP3 inflammasome expression, compared to AAV-GFP controls. These findings suggest that TXNIP is a key regulator of ASD-induced pulmonary inflammation.

BackgroundPlasmodium falciparum is the most lethal malaria parasite. Recent phase 1b vaccine trials using P. falciparum reticulocyte binding protein homolog 5 (PfRh5) demonstrated safety and promising efficacy in preventing merozoite invasion. PfRh5 has emerged as a strong vaccine candidate due to its essential role in merozoite invasion and limited sequence variation. For effective malaria vaccine development, especially in high-transmission settings, strain-transcending activity must be considered. Ongoing monitoring of antigenic variation and natural immune responses is important to estimate vaccine efficacy across geographically diverse populations.MethodsSamples for this study were collected from four villages in each of the Kigoma and Geita regions, known malaria transmission hotspots in Tanzania. This community-based cross-sectional study was conducted from December 2022 to July 2023. Genetic variation and natural selection pressure on pfrh5 were analyzed in 164 asymptomatic P. falciparum isolates. The humoral immune response to PfRh5 was also assessed using a protein microarray with 242 sera samples from asymptomatic patients in the same population. Finally, a correlation analysis was conducted to compare pfrh5 genetic variation with the humoral immune response.ResultsThe results revealed that pfrh5 was well conserved, but novel non-synonymous mutations were found at D65H, H170N, and I227M. Additionally, natural selection metrics indicated the potential for positive selection and a recent population expansion of PfRh5 in the study area, both of which could influence vaccine effectiveness. Antigenicity screening revealed variable sensitivity, ranging from 3.3% in Bunyambo to 82.8% in Rwantaba, with no significant relationship between antigenicity and parasitemia, haplotypes, or gender. However, age was significantly associated with humoral immune response (ρ = 0.170, p = 0.008).ConclusionsThese findings underscore the need for future PfRh5-based vaccines to consider for increasing genetic variation and geographical differences in humoral immune responses.

Abstract Background Elevated FSH often occurs in women of advanced maternal age (AMA, age ≥ 35) and in infertility patients undergoing controlled ovarian stimulation (COS). There is controversy on whether high endogenous FSH contributes to infertility and whether high exogenous FSH adversely impacts patient pregnancy rates. Methods The senescence-accelerated mouse-prone-8 (SAMP8) model of female reproductive aging was employed to assess the separate impacts of age and high FSH activity on the percentages (%) of viable and mature ovulated oocytes recovered after gonadotropin treatment. Young and midlife mice were treated with the FSH analog equine chorionic gonadotropin (eCG) to model both endogenous FSH elevation and exogenous FSH elevation. Previously we showed the activin inhibitor ActRIIB:Fc increases oocyte quality by preventing chromosome and spindle misalignments. Therefore, ActRIIB:Fc treatment was performed in an effort to increase % oocyte viability and % oocyte maturation. Results The high FSH activity of eCG is ootoxic to ovulatory oocytes, with greater decreases in % viable oocytes in midlife than young mice. High FSH activity of eCG potently inhibits oocyte maturation, decreasing the % of mature oocytes to similar degrees in young and midlife mice. ActRIIB:Fc treatment does not prevent eCG ootoxicity, but it restores most oocyte maturation impeded by eCG. Conclusions FSH ootoxicity to ovulatory oocytes and FSH maturation inhibition pose a paradox given the well-known pro-growth and pro-maturation activities of FSH in the earlier stages of oocyte growth. We propose the FOOT Hypothesis (“FSH OoToxicity Hypothesis), that FSH ootoxicity to ovulatory oocytes comprises a new driver of infertility and low pregnancy success rates in DOR women attempting spontaneous pregnancy and in COS/IUI patients, especially AMA women. We speculate that endogenous FSH elevation also contributes to reduced fecundity in these DOR and COS/IUI patients. Restoration of oocyte maturation by ActRIB:Fc suggests that activin suppresses oocyte maturation in vivo. This contrasts with prior studies showing activin A promotes oocyte maturation in vitro. Improved oocyte maturation with agents that decrease endogenous activin activity with high specificity may have therapeutic benefit for COS/IVF patients, COS/IUI patients, and DOR patients attempting spontaneous pregnancies.

This study compared glycosylated hemoglobin (HbA1c) levels in the first and second trimesters of pregnancy and assessed maternal and neonatal outcomes according to HbA1c variations among women with pregestational diabetes. This retrospective, multicenter Korean study involved mothers with diabetes who had given birth in 17 hospitals. A total of 292 women were divided into three groups based on HbA1c levels during the first and second trimesters: women with HbA1c levels maintained at

Xanthogranulomatous (XG) inflammatory disease is a rare benign disease involving various organs, including the gallbladder, bile duct, pancreas, spleen, stomach, small bowel, colon, appendix, kidney, adrenal gland, urachus, urinary bladder, retroperitoneum, and female genital organs. The imaging features of XG inflammatory disease are nonspecific, usually presenting as a heterogeneous solid or cystic mass. The disease may also extend to adjacent structures. Due to its aggressive nature, it is occasionally misdiagnosed as a malignant neoplasm. Herein, we review the radiological features and clinical manifestations of XG inflammatory diseases in various organs of the abdomen and pelvis.

A vanishing twin (VT) is the early demise of a twin fetus. It is estimated to occur in 20–30% of pregnancies associated with assisted reproductive technology. VT becomes increasingly prominent when assisted fertilization is used, because one or more embryos are transferred to the uterus. Maternal serum screening tests during pregnancy can screen for trisomy chromosomes 21, 18, and 13 and are divided into first- and second-trimester tests. In singleton pregnancies, the first trimester screening test is performed at 11–13 weeks and 6 days of gestation. It consists of two serum markers, pregnancy-associated plasma protein A and β-human chorionic gonadotropin (β-hCG), and measures nuchal translucency thickness. The second-trimester screening test was performed at 15–20 weeks and 6 days of gestation. It consists of four serum markers: alpha-fetoprotein, β-hCG, unconjugated estriol, and inhibin A. More effective screening for trisomy 21 in singleton pregnancies is achieved by analyzing cell-free DNA in the maternal blood. A VT includes a demise of the fetus. Although it affects maternal serum markers, it has not been corrected. Five studies examined the effect of VT on maternal serum markers, but the results were controversial. This study aimed to review the patterns of changes in maternal serum markers in VTs, interpret prenatal tests for pregnant women with VTs in clinical practice, and consider what information should be provided.

Asian sand dust (ASD), generated from the deserts of China and Mongolia, affects Korea and Japan during spring and autumn, causing harmful effects on various bio-organs, including the respiratory system, due to its irritants such as fine dust, chemicals, and toxic materials. Here, we investigated the therapeutic effects of silibinin against ASD-induced airway inflammation using mouse macrophage-like cell line RAW264.7 and a murine model. ASD was intranasally administered to mice three times a week and silibinin was administered for 6 days by oral gavage. In ASD-stimulated RAW264.7 cells, silibinin treatment decreased tumor necrosis factor-α production and reduced the expression of p-p65NF-κB, p-p38, and cyclooxygenase (COX)-2, while increasing heme oxygenase (HO)-1 expression. In ASD-exposed mice, silibinin administration reduced inflammatory cell count and cytokines in bronchoalveolar lavage fluid and decreased inflammatory cell infiltration in lung tissue. Additionally, silibinin lowered oxidative stress, as evidenced by decreased 8-hydroxy-2’-deoxyguanosin (8-OHdG) expression and increased HO-1 expression. The expression of inflammatory-related proteins, including p-p65NF-κB, COX-2, and p-p38, was markedly reduced by silibinin administration. Overall, silibinin treatment reduced the expression of p-p65NF-κB, COX-2, and p-p38 in response to ASD exposure, while increasing HO-1 expression both in vitro and in vivo. These findings suggest that silibinin mitigates pulmonary inflammation caused by ASD exposure by reducing inflammatory signaling and oxidative stress, indicating its potential as a therapeutic agent for ASD-induced pulmonary inflammation.

Titanium dioxide nanoparticles (TiO2NPs) are used in products that are applied to the human body, such as cosmetics and food, but their biocompatibility remains controversial. Pycnogenol (PYC), a natural extract of pine bark, exerts anti-inflammatory and antioxidant effects. In this study, we investigated whether PYC effectively alleviates pulmonary toxicity induced by airway exposure to TiO2NPs, and the beneficial effects of PYC were explained through the analysis of changes to the mechanism of cytotoxicity. TiO2NPs induced pulmonary inflammation and mucus production, increased the levels of malondialdehyde, and upregulated thioredoxin-interacting protein (TXNIP) and cleaved-caspase 3 (Cas3) in the lungs of mice. However, PYC treatment reduced the levels of all toxicity markers of TiO2NPs and restored glutathione levels. These antioxidant and anti-inflammatory effects of PYC were also demonstrated in TiO2NP-exposed human airway epithelial cells by increasing the mRNA levels of antioxidant enzymes and decreasing the expression of TXNIP, cleaved-Cas3, and inflammatory mediators. Taken together, our results showed that PYC attenuated TiO2NP-induced lung injury via TXNIP downregulation. Therefore, our results suggest the potential of PYC as an effective anti-inflammatory and antioxidant agent against TiO2NP-induced pulmonary toxicity.

Myxoid liposarcoma is an extremely rare malignant breast tumor. We report the case of a 44-year-old woman who had myxoid liposarcoma of the breast with a history of phyllodes tumor and describe the imaging findings on US, mammography, and MRI. Before surgery, the mass was considered to be a recurrent phyllodes tumor. However, using US, we retrospectively identified some differences between myxoid liposarcomas and phyllodes tumors.

Objective The air pollution on pregnancy outcome (APPO) study is a prospective hospital-based cohort study designed to investigate the maternal and fetal effects of a particulate matter with an aerodynamic below 10 μm (PM10) and PM2.5 (below 2.5 μm) exposure. This study aims to analyze a relationship between particulate matter and adverse pregnancy outcomes and to find related biomarkers and develop management guidelines. Methods About 1,200 pregnant women are recruited for 3 years (from January 2021 to December 2023) from seven university hospitals to investigate the effects of particulate matter on pregnancy complications and adverse pregnancy outcomes. We collect biological samples by 5 mL of maternal venous blood and 15 mL of urine in each trimester of pregnancy, and 5 mL of umbilical cord blood and 2×2×2 cm of placental tissue are collected after delivery. In addition, by applying PM10 and PM2.5 concentration values and time-activity patterns from the time weighted average model, the individual predicted exposure of air pollution for the pregnant women are obtained. Results The average exposure of PM10 and PM2.5 of the participants in the entire period of pregnancy, was exceeded the World Health Organization air quality guidelines (an annual level, PM10 >15 μg/m3, PM2.5 >5 μg/m3). Moreover, it was revealed that the PM concentration was increasing toward the 3rd trimester of pregnancy. Conclusion The APPO study will be able to identify the degree of exposure to air pollution in pregnant women and use it as basic data for estimating individual exposure to particulate matter. And the results of the APPO study will facilitate in the development of health management for pregnant women against air pollution.

Malaria eradication efforts in resource-limited areas require a rapid, economical, and accurate tool for detecting of the low parasitemia. The malaria rapid diagnostic test (mRDT) is the most suitable for on-site detection of the deadliest form of malaria, Plasmodium falciparum. However, the deletions of histidine rich protein 2 and 3 genes are known to compromise the effectiveness of mRDT. One of the approaches that have been explored intensively for on-site diagnostics is the loop-mediated isothermal amplification (LAMP). LAMP is a one-step amplification that allows the detection of Plasmodium species in less than an hour. Thus, this study aims to present a new primer set to enhance the performance of a colorimetric LAMP (cLAMP) for field application. The primer binding regions were selected within the A-type of P. falciparum 18S rRNA genes, which presents a dual gene locus in the genome. The test result of the newly designed primer indicates that the optimal reaction condition for cLAMP was 30 minutes incubation at 65°C, a shorter incubation time compared to previous LAMP detection methods that typically takes 45 to 60 minutes. The limit of detection (LoD) for the cLAMP using our designed primers and laboratory-grown P. falciparum (3D7) was estimated to be 0.21 parasites/μL which was 1,000-fold higher than referencing primers. Under optimal reaction condition, the new primer sets showed the sensitivity (100%, 95% CI: 80.49-100%) and specificity (100%, 95% CI: 94.64-100%) with 100% (95% CI: 95.70-100%) accuracy on the detection of dried blood spots from Malawi (n = 84). Briefly, the newly designed primer set for P. falciparum detection exhibited high sensitivity and specificity compared to referenced primers. One great advantage of this tool is its ability to be detected by the naked eye, enhancing field approaches. Thus, this tool has the potential to be effective for accurate early parasite detection in resource-limited endemic areas.

Abstract Background Babesia is an intraerythrocytic parasite often misdiagnosed as a malaria parasite, leading to inappropriate treatment of the disease especially in co-endemic areas. In recent years, optical diffraction tomography (ODT) has shown great potential in the field of pathogen detection by quantification of three-dimensional (3D) imaging tomograms. The 3D imaging of biological cells is crucial to investigate and provide valuable information about the mechanisms behind the pathophysiology of cells and tissues. Methods The early ring stage of P. falciparum were obtained from stored stock of infected RBCs and of B. microti were obtained from infected patients during diagnosis. The ODT technique was applied to analyze and characterize detailed differences between P. falciparum and B. microti ring stage at the single cell level. Based on 3D quantitative information, accurate measurement was performed of morphological, biochemical, and biophysical parameters. Results Accurate measurements of morphological parameters indicated that the host cell surface area at the ring stage in B. microti was significantly smaller (140.2 ± 17.1 µm2) than that in P. falciparum (159.0 ± 15.2 µm2), and sphericities showed higher levels in B. microti-parasitized cells (0.66 ± 0.05) than in P. falciparum (0.60 ± 0.04). Based on biochemical parameters, host cell hemoglobin level was significantly higher and membrane fluctuations were respectively more active in P. falciparum-infected cells (30.25 ± 2.96 pg; 141.3 ± 24.68 nm) than in B. microti (27.28 ± 3.52 pg; 110.1 ± 38.83 nm). The result indicates that P. falciparum more actively altered host RBCs than B. microti. Conclusion Although P. falciparum and B. microti often show confusable characteristics under the microscope, and the actual three-dimensional properties are different. These differences could be used in differential clinical diagnosis of erythrocytes infected with B. microti and P. falciparum. Graphical Abstract

Asian sand dust (ASD), generally produced in East Asia, including China, Japan, and Korea, directly leads to the development of pulmonary disease and exacerbates underlying pulmonary diseases. Loranthus tanakae Franch. and Sav. is a traditional herbal medicine applied to improve various inflammatory conditions. Here, we evaluated the curative properties of L. tanakae ethanol extract (LTE) against pulmonary inflammation caused by ASD. Additionally, to investigate the mechanism of action of LTE, we performed network pharmacological analysis. ASD was administrated on day 1, 3, and 5 by intranasal instillation, and LTE was orally administered for 6 days. Administration of LTE significantly decreased inflammatory cytokines and the number of inflammatory cells in bronchoalveolar lavage fluid, which was accompanied by a decrease in inflammatory cell accumulation in pulmonary tissue. Administration of LTE decreased the expression of cyclooxygenase2 and matrix metalloproteinase-9 in mice exposed to ASD with the decline in p65 phosphorylation. Additionally, administration of LTE significantly elevated hemeoxygenase (HO)-1 expression in the pulmonary tissue of mice exposed to ASD. These results were consistent with the data of network pharmacological analysis. This experiment showed that LTE attenuated pulmonary inflammation caused by ASD via inhibition of NF-κB and elevation of HO-1. Therefore, LTE may have potential as a therapeutic agent to treat pulmonary inflammation caused by ASD.

Abstract Background Myostatin (MSTN) is a transforming growth factor-ß superfamily member that acts as a major regulator of skeletal muscle mass. GDF-11, which is highly related to MSTN, plays multiple roles during embryonic development, including regulating development of the axial skeleton, kidneys, nervous system, and pancreas. As MSTN and GDF-11 share a high degree of amino acid sequence identity, behave virtually identically in cell culture assays, and utilize similar regulatory and signaling components, a critical question is whether their distinct biological functions result from inherent differences in their abilities to interact with specific regulatory and signaling components or whether their distinct biological functions mainly reflect their differing temporal and spatial patterns of expression. Methods We generated and characterized mice in which we precisely replaced in the germline the portion of the Mstn gene encoding the mature C-terminal peptide with the corresponding region of Gdf11. Results In mice homozygous for the knock-in allele, all of the circulating MSTN protein was replaced with GDF-11, resulting in ~ 30–40-fold increased levels of circulating GDF-11. Male mice homozygous for the knock-in allele had slightly decreased muscle weights, slightly increased weight gain in response to a high-fat diet, slightly increased plasma cholesterol and HDL levels, and significantly decreased bone density and bone mass, whereas female mice were mostly unaffected. Conclusions GDF-11 appears to be capable of nearly completely functionally replacing MSTN in the control of muscle mass. The developmental and physiological consequences of replacing MSTN with GDF-11 are strikingly limited.

During routine antenatal ultrasound examinations, an ovarian mass can be found incidentally. In clinical practice, the differential diagnosis between benign and malignant ovarian masses is essential for planning further management. Ultrasound imaging has become the most popular diagnostic tool during pregnancy, with the recent development of ultrasonography. In non-pregnant women, several methods have been used to predict malignant ovarian masses before surgery. The International Ovarian Tumor Analysis (IOTA) group reported several scoring systems, such as the IOTA simple rules, IOTA logistic regression models, and IOTA assessment of different NEoplasias in the adneXa. Other researchers have also evaluated the malignancy of ovarian masses before surgery using scoring systems such as the Sassone score, pelvic mass score, DePriest score, Lerner score, and Ovarian-Adnexal Reporting and Data System. These researchers suggested specific features of ovarian masses that can be used for differential diagnosis, including size, proportion of solid tissue, papillary projections, inner wall structure, locules, wall thickness, septa, echogenicity, acoustic shadows, and presence of ascites. Although these factors can also be measured in pregnant women using ultrasound, only a few studies have applied ovarian scoring systems in pregnant women. In this article, we reviewed various scoring systems for predicting malignant tumors of the ovary and determined whether they can be applied to pregnant women.

Korea has entered a stage of low fertility, with a total fertility rate of 1.178 in 2002 and 0.92 in 2019. The low birth rate has led to the closure of obstetric hospitals and clinics from 1,371 maternity health facilities in 2003 to 541 in 2019, which is 39.5% compared to 2003. Since 2011, the Ministry of Health and Welfare has been operating an “Obstetrically Underserved Areas Support Project,” however, a shortage of obstetrician-gynecologists (OB/GYNs) who can participate in labor and delivery is a major problem. In 2019, there were 5,800 OB/GYNs practicing. Of these, 4,225 (72.8%) were working in obstetrics-gynecology hospitals, each responsible for 2,855 fertile women. Their average age was 51.8 years. A total of 2,659 (45.9%) worked in clinics and 3,110 (73.6%) were working in metropolitan districts. Only 124 OB/GYNs (2.9%) worked in vulnerable rural areas. OB/GYNs working in obstetric hospitals were responsible for 113.8 newborns in 2019. Their average age was 50.1 years. Of them, 67.4% were working in hospitals, 74.1% in urban areas, and only 60 specialists (2.3%) were working in rural areas. To establish a safe childbirth environment during an era of low fertility, it is important to have obstetricians in charge of childbirth. The government should establish a comprehensive long-term plan to resolve the shortage of OB/GYNs.

Neonatal brachial plexus injury (NBPI) causes disabling and incurable muscle contractures that result from impaired longitudinal growth of denervated muscles. This deficit in muscle growth is driven by increased proteasome-mediated protein degradation, suggesting a dysregulation of muscle proteostasis. The myostatin (MSTN) pathway, a prominent muscle-specific regulator of proteostasis, is a putative signaling mechanism by which neonatal denervation could impair longitudinal muscle growth, and thus a potential target to prevent NBPI-induced contractures. Through a mouse model of NBPI, our present study revealed that pharmacologic inhibition of MSTN signaling induces hypertrophy, restores longitudinal growth, and prevents contractures in denervated muscles of female but not male mice, despite inducing hypertrophy of normally innervated muscles in both sexes. Additionally, the MSTN-dependent impairment of longitudinal muscle growth after NBPI in female mice is associated with perturbation of 20S proteasome activity, but not through alterations in canonical MSTN signaling pathways. These findings reveal a sex dimorphism in the regulation of neonatal longitudinal muscle growth and contractures, thereby providing insights into contracture pathophysiology, identifying a potential muscle-specific therapeutic target for contracture prevention, and underscoring the importance of sex as a biological variable in the pathophysiology of neuromuscular disorders.

In modern buildings, indoor humidity must be effectively controlled for thermal comfort and to inhibit the breeding of mold and mildew. To exclude the dependence on additional regeneration heat source for desiccant cooling system, this field study used heat pump-assisted hybrid desiccant cooling (HPDC) systems, which place the evaporator upstream of dehumidification side of the desiccant wheel to perform pre-cooling and pre-dehumidification. The main purpose was to investigate the thermal environment control and energy-saving effects of HPDC systems under different load pattern scenarios; Field studies were conducted in residential buildings, public space, and classrooms. When operating in the first scenario, the electricity consumption of the HPDC system was 37.4% and 14% lower than that of conventional electric heat pumps (EHPs) under different wall thermal-storage conditions. In the second scenario, high dehumidification load led to large adsorption heat, causing indoor temperature to rise continually until the indoor humidity reached the design level. Through the field study in the classroom, the dehumidification mode and cooling mode switching approach can effectively improve indoor temperature control problems and reduce energy consumption by 14% compared to EHP. This field study covers possible application scenarios for HPDC systems, demonstrating the feasibility of replacing conventional air conditioning.

The prevalence of asthma is gradually increasing, and endangers human health. Many therapeutic agents have been developed to address this concern. Cinnamomum cassia (L.) J.Presl is a traditional herbal remedy in China, Japan, and Korea and used mainly to control common cold, cough, pneumonitis and fever in Donguibogam, a medical encyclopedia of Korea. Therefore, we investigated whether C. cassia (L.) J.Presl extract (CCE) confers protective effects on asthma model induced by ovalbumin (OVA). The animals were received intraperitoneal administration of OVA on day 1 and 14, and then subjected to OVA inhalation from day 21–23. They were orally treated CCE (30 and 100 mg/kg) from day 18–23. CCE administration decreased allergic responses, including airway hyperresponsiveness, eosinophilia, inflammatory cytokine production, and immunoglobulin E in OVA-exposed mice, along with the decline in inflammatory cell count and mucus secretion in respiratory tract. Additionally, CCE suppressed MAPK phosphorylation and MMP-9 expression in OVA-exposed mice. Overall, CCE treatment attenuated allergic responses induced by OVA exposure, which may be connected to the suppression of MAPK phosphorylation.

Building on the known role of BMP signalling in implantation, the authors define the role of uterine ACVR2A and ALK3 (via SMAD1/5) in vivo in regulating murine endometrial receptivity and embryo implantation.

Background: Pyometra is defined as an accumulation of purulent material in the uterine cavity. It is caused by natural drainage impairment within the cervix and occurs predominantly in elderly women. In this study, we aimed to investigate the clinical characteristics and recurrent risk of pyometra. Methods: Data for patients diagnosed with pyometra between 2010 and 2021 were retrospectively reviewed. Basic patient characteristics, including age, underlying disease, management, chief complaint, antibiotics, and isolated organisms, were investigated. The risk of recurrence of pyometra was assessed using multivariate logistic regression analyses. In total, 65 patients with pyometra were included in this study. Results: The mean age of the patients was 75.8 ± 16.4 years. About half of the patients had been admitted to a nursing hospital due to poor mobility, and 61.5% of the patients had an Eastern Cooperative Oncology Group performance score of 2 or higher. The most prevalent presenting symptoms were vaginal discharge (73.9%) and fever (16.9%). Forty-eight (75.0%) patients underwent drainage, and seven (10.9%) underwent hysterectomy. Escherichia coli accounted for the most cases (36.9%), followed by Klebsiella pneumoniae (20.0%). Overall, 17 patients were extended-spectrum β-lactamase positive. Recurrence after drainage occurred in 16 (24.6%) of the 65 patients, and two patients died from septic shock. The isolation of Klebsiella pneumoniae was identified as a significant risk factor for recurrence (odds ratio (OR): 4.71; 95% confidence interval (CI): 1.09–20.47; p < 0.05). Conclusions: Because pyometra often occurs in elderly patients with chronic diseases, it is important to pursue appropriate treatment and prevention of recurrence to decrease the morbidity and mortality associated with this condition. The isolated organisms should be considered as a predisposing factor for recurrent pyometra.

Abstract Background This study introduced machine learning approaches to predict newborn’s body mass index (BMI) based on ultrasound measures and maternal/delivery information. Methods Data came from 3159 obstetric patients and their newborns enrolled in a multi-center retrospective study. Variable importance, the effect of a variable on model performance, was used for identifying major predictors of newborn’s BMI among ultrasound measures and maternal/delivery information. The ultrasound measures included biparietal diameter (BPD), abdominal circumference (AC) and estimated fetal weight (EFW) taken three times during the week 21 - week 35 of gestational age and once in the week 36 or later. Results Based on variable importance from the random forest, major predictors of newborn’s BMI were the first AC and EFW in the week 36 or later, gestational age at delivery, the first AC during the week 21 - the week 35, maternal BMI at delivery, maternal weight at delivery and the first BPD in the week 36 or later. For predicting newborn’s BMI, linear regression (2.0744) and the random forest (2.1610) were better than artificial neural networks with one, two and three hidden layers (150.7100, 154.7198 and 152.5843, respectively) in the mean squared error. Conclusions This is the first machine-learning study with 64 clinical and sonographic markers for the prediction of newborns’ BMI. The week 36 or later is the most effective period for taking the ultrasound measures and AC and EFW are the best predictors of newborn’s BMI alongside gestational age at delivery and maternal BMI at delivery.

Abstract Beauveria bassiana is a species complex whose isolates show considerable natural genetic variability. However, little is known about how this genetic diversity affects the fungus performance. Herein, we characterized the diversity of genes involved in various mechanisms of the infective cycle of 42 isolates that have different growth rates, thermotolerance and virulence. The analysed genes showed general genetic diversity measured as non-synonymous changes (NSC) and copy number variation (CNV), with most of them being subjected to positive episodic diversifying selection. Correlation analyses between NSC or CNV and the isolate virulence, thermotolerance and growth rate revealed that various genes shaped the biological features of the fungus. Lectin-like, mucin signalling, Biotrophy associated and chitinase genes NSCs correlated with the three biological features of B. bassiana. In addition, other genes (i.e. DNA photolyase and cyclophilin B) that had relatively conserved sequences, had variable CNs across the isolates which were correlated with the variability of either virulence or thermotolerance of B. bassiana isolates. The data obtained is important for a better understanding of population structure, ecological and potential impact when isolates are used as mycoinsecticides and can justify industrialization of new isolates.

Abstract Background Insect-killing fungal species, Beauveria bassiana, is as an environment-friendly pest management tool, and many isolates are on the track of industrialization. However, some of B. bassiana isolates show similar morphology and virulence against insect pests, and so it is hard to differentiate them. Herein we used two patented isolates, ERL836 and JEF-007, and investigated their virulence against western flower thrips, Frankliniella occidentalis, and further analyzed genome structures and transcriptional responses when interacting with cuticles of thrips to see possible differences on the initial step of fungal infection. Results The two isolates showed no significant differences in fungal growth, conidial production, and virulence against thrips, and they were structurally similar in genome. But, in transcription level, ERL836 appeared to infect thrips easily, while JEF-007 appeared to have more difficulty. In the GO analysis of ERL836 DEGs (differentially expressed genes), the number of up-regulated genes was much larger than that of down-regulated genes, when compared to JEF-007 DEGs (more genes down-regulated). Interestingly, in the enrichment analysis using shared DEGs between two infecting isolates, plasma membrane-mediated transporter activity and fatty acid degradation pathway including cytochrome P450 were more active in infecting ERL836. Conclusion The two B. bassiana isolates had similar morphology and virulence as well as genome structure, but in transcription level they differently interacted with the cuticle of western flower thrips. This comparative approach using shared DEG analysis could be easily applied to characterize the difference of the two B. bassiana isolates, JEF-007 and ERL836.

The objective of this study was to investigate the influence of increasing carcass weight (CW) on meat quality traits including meat color, water-holding capacity (WHC), tenderness, backfat thickness and intramuscular fat (IMF) content of pork loin. A total of 96 pork carcasses (48 LYD [Landrace × Yorkshire × Duroc] barrows and gilts) were selected at a commercial slaughterhouse. Each gender had commercial CW (≤ 90 kg), heavy CW (91–100 kg) and very heavy CW (> 100 kg) (16 carcasses from each CW group). Loin cuts (Longissimus lumborum) were excised to investigate meat color (CIE L*a*b*), drip loss, cooking loss, released water, Warner-Bratzler shear force (WBSF), and IMF content. Backfat thickness and IMF content of pork loin samples were significantly (p < 0.05) increased with increasing CW, although there was no significant difference in ultimate pH (pHu). CIE a* increased significantly (p < 0.05) with increasing CW, while there were no significant differences in CIE L* or CIE b* among CW groups. Although all WHC measures showed no significant differences among CW groups, WBSF increased significantly (p < 0.01) with increasing CW. Sensory flavor score was significantly increased while panel score for tenderness was decreased significantly (p < 0.001) with increasing CW. Consequently, CW had a positive correlation with flavor but negative correlation with tenderness. These results indicate that the increased IMF content improves flavor, juiciness and palatability, although tenderness deteriorates with increasing CW.

Root-feeding Scarabaeidae, particularly white grubs are considered among the most harmful coleopteran insect pests in turfgrass. In this work, sixteen entomopathogenic fungal species were assayed against flower chafer beetle, Protaetia brevitarsis (Coleoptera: Scarabaeidae) and Metarhizium anisopliae JEF-314 showed high virulence. The control ability of the isolate JEF-314 has been in detail tested for a model insect flower chafer beetle. Further analyses showed insect stage-dependent virulence where the fungal virulence was the highest against smaller instar larvae. Additionally, we confirmed that millet-based solid cultured granule was effective against the soil-dwelling larval stage. The isolate also showed a similar ability for a representative pest (Popillia spp.) in laboratory conditions. Our results clearly suggest a high potential of M. anisopliae JEF-314 to control the flower chafer beetle, possibly resulting in controlling of root-feeding white grubs in turfgrass. Based on the insect life cycle and susceptibility to the fungus, late spring and summer time would be the optimum time to apply JEF-314 granules for an effective control. Further characterization of the efficacy of the fungus under field conditions against the Scarabaeidae beetles might provide an efficient tool to control this beetle in an environment-friendly way.

Negative myoclonus (NM) is a shock-like jerky involuntary movement caused by a sudden, brief interruption of tonic muscle contraction. NM is observed in patients diagnosed with epilepsy, metabolic encephalopathy, and drug toxicity and in patients with brain lesions. A 55-year-old man presented with NM in both his arms and neck. He has taken medications containing tramadol at a dose of 80–140 mg/day for 5 days due to common cold. He had no history of seizures. Acute lesions were not observed during magnetic resonance imaging, and abnormal findings in his laboratory tests were not noted. His NM resolved completely after the discontinuation of tramadol and the oral administration of clonazepam. Our case report suggests that tramadol can cause NM in patients without seizure history or metabolic disorders, even within its therapeutic dose.

Cefepime, a widely used fourth-generation cephalosporin, has been reported to cause neurotoxicity because it crosses the blood-brain barrier. Although cefepime-induced neurotoxicity (CIN) occurs in patients with renal dysfunction administered a high dosage, CIN has also been reported in patients with normal renal function administered the appropriate dosage. CIN is characterized by toxic encephalopathy and electroencephalography abnormalities, such as triphasic wave, currently renamed as generalized periodic discharge (GPD) with triphasic morphology, and nonconvulsive status epilepticus (NCSE). Toxic encephalopathy appears 2 to 6 days after cefepime administration and disappears 3 days after discontinuation of cefepime. Electroencephalography abnormalities in most reported cases are GPD with triphasic morphology rather than NCSE. CIN is reversible in most cases if early detection and discontinuation of cefepime is possible, which is the only definitive treatment; however, anticonvulsant therapy is unnecessary except for patients with convulsive seizures or definite NCSE. Emergent hemodialysis may also be helpful in life-threatening situations.

There have been several reports of patients with isolated lesions of the cerebellar vermis presenting with clinical features similar to those of peripheral vestibulopathy. We report a case of small, isolated hematoma in the cerebellar vermis in a patient who presented with vertigo, ipsilesional nystagmus, and body lateropulsion to the contralesional side without the usual signs or symptoms of cerebellar dysfunction. Although they present with symptoms that mimic those of peripheral vestibulopathy, and brain computed tomography shows no abnormality, as there may be a small, isolated hematoma or infarction in the cerebellar vermis. Thus, brain magnetic resonance imaging should be performed in elderly patients with vascular risk factors.

Background The neurological manifestations of Sjögren’s syndrome (SjS) are nonspecific and may precede the onset of sicca symptoms. Hence, the diagnosis of SjS is often delayed. Recurrent aseptic meningitis is an uncommon neurological manifestation of primary SjS; only few cases have been reported in the medical literature. Case ReportA 54-year-old woman was admitted for recurrent aseptic meningitis. The patient had a history of two episodes of aseptic meningitis, which had occurred 12 and 7 years before this presentation. The patient had overt sicca symptoms for 5 years. SjS was diagnosed based on the results of serum autoantibody tests, Schirmer’s test, and salivary scintigraphy. We concluded that recurrent aseptic meningitis occurred as an initial presentation of primary SjS. ConclusionThis case suggest that SjS should be included in the differential diagnosis of recurrent aseptic meningitis.

Abstract Background The golden birdwing butterfly (Troides aeacus formosanus) is a rarely observed species in Taiwan. Recently, a typical symptom of nuclear polyhedrosis was found in reared T. aeacus larvae. From the previous Kimura-2 parameter (K-2-P) analysis based on the nucleotide sequence of three genes in this isolate, polh, lef-8 and lef-9, the underlying virus did not belong to any known nucleopolyhedrovirus (NPV) species. Therefore, this NPV was provisionally named “TraeNPV”. To understand this NPV, the nucleotide sequence of the whole TraeNPV genome was determined using next-generation sequencing (NGS) technology. Results The genome of TraeNPV is 125,477 bp in length with 144 putative open reading frames (ORFs) and its GC content is 40.45%. A phylogenetic analysis based on the 37 baculoviral core genes suggested that TraeNPV is a Group I NPV that is closely related to Autographa californica nucleopolyhedrovirus (AcMNPV). A genome-wide analysis showed that TraeNPV has some different features in its genome compared with other NPVs. Two novel ORFs (Ta75 and Ta139), three truncated ORFs (pcna, he65 and bro) and one duplicated ORF (38.7 K) were found in the TraeNPV genome; moreover, there are fewer homologous regions (hrs) than there are in AcMNPV, which shares eight hrs within the TraeNPV genome. TraeNPV shares similar genomic features with AcMNPV, including the gene content, gene arrangement and gene/genome identity, but TraeNPV lacks 15 homologous ORFs from AcMNPV in its genome, such as ctx, host cell-specific factor 1 (hcf-1), PNK/PNL, vp15, and apsup, which are involved in the auxiliary functions of alphabaculoviruses. Conclusions Based on these data, TraeNPV would be clarified as a new NPV species with defective AcMNPV genomic features. The precise relationship between TraeNPV and other closely related NPV species were further investigated. This report could provide comprehensive information on TraeNPV for evolutionary insights into butterfly-infected NPV.

Loranthus tanakae Franch. & Sav. found in China, Japan, and Korea is traditionally used for managing arthritis and respiratory diseases. In this study, we analyzed the components of L. tanakae 70% ethanol extract (LTE) and investigated the therapeutic effects of LTE on pulmonary inflammation using cells exposed to cigarette smoke condensate (CSC) and lipopolysaccharide (LPS) in vitro and in vivo in mice and performed a network analysis between components and genes based on a public database. We detected quercitrin, afzelin, rhamnetin 3-rhamnoside, and rhamnocitrin 3-rhamnoside in LTE, which induced a significant reduction in inflammatory mediators including interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α and inflammatory cells in CSC exposed H292 cells and in mice, accompanied by a reduction in inflammatory cell infiltration into lung tissue. In addition, LTE increased translocation into the nuclei of nuclear factor erythroid-2-related factor 2 (Nrf2). By contrast, the activation of nuclear factor (NF)-κB, induced by CSC exposure, decreased after LTE application. These results were consistent with the network pharmacological analysis. In conclusion, LTE effectively attenuated pulmonary inflammation caused by CSC+LPS exposure, which was closely involved in the enhancement of Nrf2 expression and suppression of NF-κB activation. Therefore, LTE may be a potential treatment option for pulmonary inflammatory diseases including chronic obstructive pulmonary disease (COPD).

The longhorned tick, Haemaphysalis longicornis (Acari: Ixodidae), is a hard tick and a vector for severe fever with thrombocytopenia syndrome (SFTS) virus. The number of patients infected with SFTS is rapidly increasing. Recently, the invertebrate pathogen Metarhizium anisopliae JEF-290 was reported to be useful to control the tick as an alternative to chemical acaricides, which are not easily applicable in human living areas where the tick is widely spread. In this study, we analyzed how the tick and the fungal pathogen interact at the transcriptional level. Field-collected tick nymphs were treated with JEF-290 conidia at 1 × 108 conidia/ml. In the early stage of infection with 2.5% mortality, the infected ticks were subjected to RNA sequencing, and non-infected ticks and fungal masses served as controls. Fungus and tick genes were mostly up-regulated at the early stage of infection. In the gene set enrichment analysis of the infecting fungus, catabolic processes that included lipids, phospholipids, and detoxification processes, the response to oxidative stress, and toxic substances were significantly up-regulated. In this fungal up-regulation, various lipase, antioxidant enzyme, and hydrolase genes were highly transcribed. The gene set enrichment analysis of the infected tick showed that many peptide synthesis processes including translation, peptide metabolism, ribonucleotide metabolism, and energy production processes that included ATP generation and ADP metabolism were significantly up-regulated. Structurally, mitochondria and ribosome subunit genes in ticks were highly transcribed to upregulate these processes. Together these results indicate that JEF-290 initiates process that infects the tick while the tick actively defends against the fungal attack. This work provides background to improve our understanding of the early stage of fungal infection in longhorned tick.

This study was a multicenter retrospective cohort study of term nulliparous women who underwent labor, and was conducted to develop an automated machine learning model for prediction of emergent cesarean section (CS) before onset of labor. Nine machine learning methods of logistic regression, random forest, Support Vector Machine (SVM), gradient boosting, extreme gradient boosting (XGBoost), light gradient boosting machine (LGBM), k-nearest neighbors (KNN), Voting, and Stacking were applied and compared for prediction of emergent CS during active labor. External validation was performed using a nationwide multicenter dataset for Korean fetal growth. A total of 6549 term nulliparous women was included in the analysis, and the emergent CS rate was 16.1%. The C-statistics values for KNN, Voting, XGBoost, Stacking, gradient boosting, random forest, LGBM, logistic regression, and SVM were 0.6, 0.69, 0.64, 0.59, 0.66, 0.68, 0.68, 0.7, and 0.69, respectively. The logistic regression model showed the best predictive performance with an accuracy of 0.78. The machine learning model identified nine significant variables of maternal age, height, weight at pre-pregnancy, pregnancy-associated hypertension, gestational age, and fetal sonographic findings. The C-statistic value for the logistic regression machine learning model in the external validation set (1391 term nulliparous women) was 0.69, with an overall accuracy of 0.68, a specificity of 0.83, and a sensitivity of 0.41. Machine learning algorithms with clinical and sonographic parameters at near term could be useful tools to predict individual risk of emergent CS during active labor in nulliparous women.

Negative myoclonus (NM) is a jerky, shock-like involuntary movement caused by a sudden, brief interruption of muscle contraction. An 80-year-old man presented with multifocal NM and confusion. Two days before the onset of NM, he commenced the intake of pregabalin at a dose of 150 mg/day for neuropathic pain. His NM resolved completely and mental status improved gradually after the administration of lorazepam intravenously and the discontinuation of pregabalin. Our study suggests that pregabalin can cause NM even in patients without a history of seizures.

Silica dioxide nanoparticles (SiONPs) have been increasingly used in various industries; however, this has raised concerns regarding their potential toxicity. SiONPs are also a major component in the Asian sand dust that causes pulmonary diseases among the general public. Melatonin exerts some inhibitory effects against lung inflammation. In this study, we explored the therapeutic properties of melatonin against lung inflammation using an SiONPs-induced lung inflammation murine model and SiONPs-stimulated H292 cells, human airway epithelial cell line, by focusing on the involvement of thioredoxin-interacting protein (TXNIP) in the modulation of the MAPKs/AP-1 axis. We induced an inflammatory response by exposing mouse lungs and the H292 cells to SiONPs and confirmed the anti-inflammatory effect of melatonin. Melatonin inhibited the expression of various inflammatory mediators, including TNF-α, IL-6, and IL-1β, in SiONPs-exposed mice and SiONPs-stimulated H292 cells; this inhibition contributed to a decline in inflammatory cell accumulation in the lung tissues. Furthermore, melatonin treatment decreased the expression of MAPKs and AP-1 by downregulating TXNIP, eventually decreasing the production of SiONPs-induced inflammatory mediators. Overall, these data suggest that melatonin reduces SiONPs-induced lung inflammation by downregulating the TXNIP/MAPKs/AP-1 signalling pathway, thereby supporting the use of melatonin as an effective approach to control SiONPs-induced lung inflammation.

The main objective of this study was to incorporate soy-based textured vegetable protein (TVP) into beef patties in different quantities (10–40%) and compare various characteristics of these innovative formulations with a regular beef patty as a control. Incorporation of 10–40% TVP resulted in significantly lower (p < 0.05) moisture and fat contents, while higher crude fiber contents were detected compared to beef as the control. In addition, cooked patties showed higher pH levels (p < 0.05), with color coordinates expressing lighter, yellowish, and slightly redder indices than raw patties. Similarly, a plant protein that includes TVP minimizes (p < 0.05) WHC (water holding capacity), both RW% (release water) and CL% (cooking loss). Furthermore, hardness, cohesiveness, and thickness were reduced significantly (p < 0.05), while gumminess and chewiness increased (p < 0.05) considerably with the substitution of TVP (10–40%) compared to the control. Patties made without TVP received higher scores for sourness, bitterness, umami, and richness than the rest of the formulations. However, a higher tendency was detected for sourness, astringency, umami, and saltiness values with increasing additions of TVP. Nevertheless, hierarchical clustering revealed that the largest group of fatty acid profiles, including palmitoleic acid (C16:1), stearic acid (C18:0), and palmitic acid (C16:0), was slightly reduced with the addition of TVP, while arachidic acid (C20:0), lauric acid (C12:0), and oleic acid (C18:1) increased moderately with increasing levels of TVP. Meanwhile, the second-largest cluster that included linoleic acid (C18:2), arachidonic acid (C20:4), and linolenic acid (C18:3) increased enormously with higher levels of TVP incorporation. Taken together, it is suggested that incorporation of TVP up to 10–40% in beef patties shows promising results.

Cimicifugae Rhizoma has been used as a medicinal herb for fever, pain, and inflammation in East Asia. We conducted this study because the effect of Cimicifugae Rhizoma extract (CRE) on allergic asthma has not yet been evaluated. To induce allergic airway inflammation, we intraperitoneally injected ovalbumin (OVA) mixed with aluminum hydroxide into mice twice at intervals of 2 weeks (Days 0 and 14) and then inhaled them thrice with 1% OVA solution using a nebulizer (Days 21 to 23). CRE (30 and 100 mg/kg) was administered orally daily for 6 days (Days 18 to 23). The mice showed remarkable reduction in allergic inflammation at 100 mg/kg of CRE, as evidenced by decreased inflammatory cell counts, pro-inflammatory cytokine levels, OVA-specific immunoglobulin E level, airway hyperresponsiveness, and production of mucus. Additionally, these effects were involved with the enhancement of heme oxygenase-1 (HO-1), NAD(P)H: quinone oxidoreductase (NQO1), and nuclear factor erythroid 2-related factor 2 (Nrf2) expression and reduction of nuclear factor-κB (NF-κB) phosphorylation and matrix metalloproteinase-9 expression. Our findings indicated that CRE effectively protected against OVA-induced inflammation and oxidative stress via upregulation of the Nrf2/HO-1/NQO1 signaling and downregulation of NF-κB phosphorylation in asthma caused by OVA.

Chronic obstructive pulmonary disease (COPD) is a significant disease threatening human health. Currently, roflumilast, a phosphodiesterase (PDE)4 inhibitor, is recommended as a therapeutic agent for COPD. In this study, we investigated the therapeutic effects of melatonin against COPD, focusing on determining whether it is a PDE4 inhibitor via in vivo and in vitro experiment using cigarette smoke (CS) and cigarette smoke condensate (CSC), respectively. In the in vivo experiments, melatonin treatment reduced inflammatory responses, including inflammatory cell counts. Melatonin treatment also suppressed the CS-exposure-induced upregulation of cytokine and matrix metalloproteinase (MMP)-9, reduced the PDE4B expression, and elevated cAMP levels. In addition, these effects were synergistic, as melatonin and roflumilast cotreatment eventually ameliorated the CS-exposure-induced worsening of lung function. In the CSC-stimulated NCI-H292 cells, melatonin inhibited elevation in the levels of inflammatory cytokines, MMP-9, and PDE4, and elevated cAMP levels. Furthermore, melatonin and roflumilast cotreatment was more effective on inflammatory responses than only melatonin or roflumilast treatment. Our results indicate that melatonin relieves inflammatory response and loss of lung function in COPD, which is associated with decreased PDE4 expression. Therefore, we suggest that melatonin is a putative candidate for the treatment of COPD.

Lactic acid bacteria (LAB) have been used for various food fermentations for thousands of years. Recently, LAB are receiving increased attention due to their great potential as probiotics for man and animals, and also as cell factories for producing enzymes, antibodies, vitamins, exopolysaccharides, and various feedstocks. LAB are safe organisms with GRAS (generally recognized as safe) status and possess relatively simple metabolic pathways easily subjected to modifications. However, relatively few studies have been carried out on LAB inhabiting plants compared to dairy LAB. Kimchi is a Korean traditional fermented vegetable, and its fermentation is carried out by LAB inhabiting plant raw materials of kimchi. Kimchi represents a model food with low pH and is fermented at low temperatures and in anaerobic environments. LAB have been adjusting to kimchi environments, and produce various metabolites such as bacteriocins, γ-aminobutyric acid, ornithine, exopolysaccharides, mannitol, etc. as products of metabolic efforts to adjust to the environments. The metabolites also contribute to the known health-promoting effects of kimchi. Due to the recent progress in multi-omics technologies, identification of genes and gene products responsible for the synthesis of functional metabolites becomes easier than before. With the aid of tools of metabolic engineering and synthetic biology, it can be envisioned that LAB strains producing valuable metabolites in large quantities will be constructed and used as starters for foods and probiotics for improving human health. Such LAB strains can also be useful as production hosts for value-added products for food, feed, and pharmaceutical industries. In this review, recent findings on the selected metabolites produced by kimchi LAB are discussed, and the potentials of metabolites will be mentioned.