A Case Study: Electrically Assisted Stress Relief Annealing for Cold-Coiled Helical Automotive Springs.

This study experimentally investigated electrically assisted (EA) stress relief annealing for cold-coiled commercial automotive springs. In EA stress relief annealing, the temperature of a spring is rapidly increased to the annealing temperature (400 °C) and is held constant for a specified time using a pulsed electric current. Experimental findings show that the effectiveness of the EA stress relief annealing is superior to that of the conventional stress relief annealing, especially in terms of process time. The present study suggests that EA stress relief annealing, with properly selected process parameters, can effectively substitute for time-consuming conventional stress relief annealing using a furnace for cold-coiled automotive springs.

Methyl lucidone inhibits airway inflammatory response by reducing TAK1 activity in human bronchial epithelial NCI-H292 cells.

Background: Methyl lucidone (ML), a methyl derivative of lucidone, has anti-inflammatory properties. However, the molecular mechanisms that reduce the inflammatory effect of ML in human lung epithelial cells remain unkown. This study aimed to elucidate the molecular mechanisms underlying the anti-inflammatory effect of ML. Methods: Four compounds (ML, methyl linderone, kanakugiol, and linderone) from Lindera erythrocarpa Makino were evaluated for their ability to reduce MUC5AC secretion levels in phorbol-12-myristate-13-acetate (PMA)-stimulated NCI-H292 cells using ELISA. The expression and secretion levels of inflammatory response-related proteins were analyzed using quantitative reverse transcription-PCR, ELISA, and western blotting. To determine whether ML directly regulates TGF-ß-activated kinase 1 (TAK1), we performed an in vitro kinase assay. Results: ML treatment effectively reduced the levels of inflammatory cytokines, including interleukin-1ß and TNF-α, increased by stimulation. Furthermore, ML downregulated the pathway cascade of both IκB kinase (IKK)/NF-κB and p38 mitogen-activated protein (MAP) kinase/CREB by inhibiting the upstream kinase TAK1. An in vitro kinase analysis confirmed that ML treatment significantly reduced the kinase activity of TAK1. Conclusion: ML pretreatment repressed the PMA-stimulated inflammation reaction by reducing the TAK1-mediated IKK/NF-κB and p38 MAP kinase/CREB signaling. These findings suggest that ML may improve respiratory health and can be used as a dietary supplement or functional food to prevent inflammatory lung diseases.

Black Ginseng Extract Exerts Potentially Anti-Asthmatic Activity by Inhibiting the Protein Kinase Cθ-Mediated IL-4/STAT6 Signaling Pathway.

Asthma is a chronic inflammatory lung disease that causes respiratory difficulties. Black ginseng extract (BGE) has preventative effects on respiratory inflammatory diseases such as asthma. However, the pharmacological mechanisms behind the anti-asthmatic activity of BGE remain unknown. To investigate the anti-asthmatic mechanism of BGE, phorbol 12-myristate 13-acetate plus ionomycin (PMA/Iono)-stimulated mouse EL4 cells and ovalbumin (OVA)-induced mice with allergic airway inflammation were used. Immune cells (eosinophils/macrophages), interleukin (IL)-4, -5, -13, and serum immunoglobulin E (IgE) levels were measured using an enzyme-linked immunosorbent assay. Inflammatory cell recruitment and mucus secretion in the lung tissue were estimated. Protein expression was analyzed via Western blotting, including that of inducible nitric oxide synthase (iNOS) and the activation of protein kinase C theta (PKCθ) and its downstream signaling molecules. BGE decreased T helper (Th)2 cytokines, serum IgE, mucus secretion, and iNOS expression in mice with allergic airway inflammation, thereby providing a protective effect. Moreover, BGE and its major ginsenosides inhibited the production of Th2 cytokines in PMA/Iono-stimulated EL4 cells. In EL4 cells, these outcomes were accompanied by the inactivation of PKCθ and its downstream transcription factors, such as nuclear factor of activated T cells (NFAT), nuclear factor kappa B (NF-κB), activator of transcription 6 (STAT6), and GATA binding protein 3 (GATA3), which are involved in allergic airway inflammation. BGE also inhibited the activation of PKCθ and the abovementioned transcriptional factors in the lung tissue of mice with allergic airway inflammation. These results highlight the potential of BGE as a useful therapeutic and preventative agent for allergic airway inflammatory diseases such as allergic asthma.

Review of Recent Prevalence of Urogenital Schistosomiasis in Sub-Saharan Africa and Diagnostic Challenges in the Field Setting.

Human schistosomiasis is one of neglected tropical diseases that remain highly prevalent in sub-Saharan Africa (SSA). Human schistosomiasis is mainly caused by two species, Schistosoma haematobium and S. mansoni, leading to urogenital and intestinal schistosomiasis, respectively. The World Health Organization (WHO) recommends mass drug administration (MDA) with praziquantel as the primary method of global intervention. Currently, MDA with praziquantel covers over half of the target population in endemic SSA countries. However, an accurate diagnosis is crucial for monitoring and evaluating the effectiveness of MDA. The standard diagnosis of both urogenital and intestinal schistosomiasis relies on the microscopic identification of eggs. However, the diagnostic sensitivity of this approach is low, especially for light or ultra-light infections. This is because Schistosoma eggs are laid inside of the venous plexus of the urinary bladder or mesenteric vein, where the adult flukes live. Approximately half of the eggs circulate in the blood vessels or are packed in neighboring tissues, while the remaining half are expelled into the lumen of the urinary bladder or intestine intermittently when the blood vessels are ruptured. In the field setting, the accuracy of any diagnostic method is critical for proper management of the intervention. The present article reviews the recent prevalence of urogenital schistosomiasis in SSA and highlights the practical limitations of diagnostic methods such as urine microscopy, urine reagent strips, molecular diagnosis, and ultrasound scanning in the field setting. Despite continuous global efforts to eliminate schistosomiasis over the past 20 years, many areas still remain endemic in SSA. No single diagnostic approach achieves acceptable sensitivity and specificity in the field setting. Therefore, any field survey should employ a combination of these methods based on the purpose of the study to accurately monitor and evaluate urogenital schistosomiasis. Based on diagnostic values and a cost-benefit analysis, a urine reagent strip test can replace urine microscopy in the field setting. The WHO criteria by ultrasound diagnosis should be updated including the echogenic snow sign and contour distortion.

What was the main factor in successful control of ascariasis in Korea?

In the l950s, under the legacy of traditional agriculture, Ascaris lumbricoides, spread epidemically in the war-bitten society of Korea. Consensus on the parasite control was drafted in the Parasite Disease Prevention Act, which passed a parliamentary agreement in 1966, and established safe disposal of feces and mass chemotherapy as control strategies. Biannual stool examinations and treating infected schoolchildren were basic scheme of the control activity through which revenue could be secured for organized business. In the 27 years following 1969, a maximum of 16 million stool examinations had been done every year. Cellophane thick smear enabled the task. The infection declined remarkably in the 1970s when industrialization and green revolution proceeded. A population study of A. lumbricoides in the late 1970s helped us better understand its epidemiology. The data also settled down the understandable protest of teachers against the repeated stool examinations. In the 9 years following 1987, the target population was gradually reduced when the egg positive rate was below 0.1%. An article in the Korean Law, stipulating obligatory stool examinations, was made optional. Although the long-term Korean effort of Ascaris control was a success, the effect of mass chemotherapy was not as succinct in terms of lowering reinfection. In the period of control, Korean agricultural technology changed, and the economy grew and supplied sanitary facilities by which the vicious cycle was disconnected. Reduction of morbidity was a benefit of mass chemotherapy, which is the only control method feasible in economically difficult countries. The most important hurdle of parasite control in the 1960s was poverty of general population and limited financial resources in Korea but the society formed a consensus on the priority of intestinal helminthiasis control during the ordeal period. The national consensus in the 1960s was the critical milestone for Ascaris control in Korea. Under the social agreement, application of timely technical and research advancements in parasitology achieved the success of ascariasis elimination. The successful experience of ascariasis elimination in Korea can be a benchmark for countries where neglected tropical diseases are endemically recycled.

Implications for selecting persistent hot spots of schistosomiasis from community- and school-based surveys in Blue Nile, North Kordofan, and Sennar States, Sudan.

In several schistosomiasis-endemic countries, the prevalence has remained high in some areas owing to reinfection despite repeated mass drug administration (MDA) interventions; these areas are referred to as persistent hot spots. Identifying hotspots is critical for interrupting transmission. This study aimed to determine an effective means of identifying persistent hot spots. First, we investigated the differences between Schistosoma haematobium and Schistosoma mansoni prevalence among school-aged children (SAC) estimated by a community-based survey, for which local key informants purposively selected communities, and a randomly sampled school-based survey. A total of 6,225 individuals residing in 60 villages in 8 districts of North Kordofan, Blue Nile, or Sennar States, Sudan participated in a community-based survey in March 2018. Additionally, the data of 3,959 students attending 71 schools in the same 8 districts were extracted from a nationwide school-based survey conducted in January 2017. The community-based survey identified 3 districts wherein the prevalence of S. haematobium or S. mansoni infection among SAC was significantly higher than that determined by the randomly sampled school survey (e.g., S. haematobium in the Sennar district: 10.8% vs. 1.1%, P<0.001). At the state level, the prevalence of schistosomiasis among SAC, as determined by the community-based survey, was consistently significantly higher than that determined by the school-based survey. Purposeful selection of villages or schools based on a history of MDA, latrine coverage, open defecation, and the prevalence of bloody urine improved the ability for identifying persistent hot spots.

Diplacone Isolated from Paulownia tomentosa Mature Fruit Induces Ferroptosis-Mediated Cell Death through Mitochondrial Ca2+ Influx and Mitochondrial Permeability Transition.

The recently defined type of cell death ferroptosis has garnered significant attention as a potential new approach to cancer treatment owing to its more immunogenic nature when compared with apoptosis. Ferroptosis is characterized by the depletion of glutathione (GSH)/glutathione peroxidase-4 (GPx4) and iron-dependent lipid peroxidation. Diplacone (DP), a geranylated flavonoid compound found in Paulownia tomentosa fruit, has been identified to have anti-inflammatory and anti-radical activity. In this study, the potential anticancer activity of DP was explored against A549 human lung cancer cells. It was found that DP induced a form of cytotoxicity distinct from apoptosis, which was accompanied by extensive mitochondrial-derived cytoplasmic vacuoles. DP was also shown to increase mitochondrial Ca2+ influx, reactive oxygen species (ROS) production, and mitochondrial permeability transition (MPT) pore-opening. These changes led to decreases in mitochondrial membrane potential and DP-induced cell death. DP also induced lipid peroxidation and ATF3 expression, which are hallmarks of ferroptosis. The ferroptosis inhibitors ferrostatin-1 and liproxstatin-1 were effective in counteracting the DP-mediated ferroptosis-related features. Our results could contribute to the use of DP as a ferroptosis-inducing agent, enabling studies focusing on the relationship between ferroptosis and the immunogenic cell death of cancer cells.

Verproside, the Most Active Ingredient in YPL-001 Isolated from Pseudolysimachion rotundum var. subintegrum, Decreases Inflammatory Response by Inhibiting PKCδ Activation in Human Lung Epithelial Cells.

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease which causes breathing problems. YPL-001, consisting of six iridoids, has potent inhibitory efficacy against COPD. Although YPL-001 has completed clinical trial phase 2a as a natural drug for COPD treatment, the most effective iridoid in YPL-001 and its mechanism for reducing airway inflammation remain unclear. To find an iridoid most effectively reducing airway inflammation, we examined the inhibitory effects of the six iridoids in YPL-001 on TNF or PMA-stimulated inflammation (IL-6, IL-8, or MUC5AC) in NCI-H292 cells. Here, we show that verproside among the six iridoids most strongly suppresses inflammation. Both TNF/NF-κB-induced MUC5AC expression and PMA/PKCδ/EGR-1-induced IL-6/-8 expression are successfully reduced by verproside. Verproside also shows anti-inflammatory effects on a broad range of airway stimulants in NCI-H292 cells. The inhibitory effect of verproside on the phosphorylation of PKC enzymes is specific to PKCδ. Finally, in vivo assay using the COPD-mouse model shows that verproside effectively reduces lung inflammation by suppressing PKCδ activation and mucus overproduction. Altogether, we propose YPL-001 and verproside as candidate drugs for treating inflammatory lung diseases that act by inhibiting PKCδ activation and its downstream pathways.

Programmatic Implications for Schistosomiasis Elimination Based on Community-Based Survey in the Blue Nile, North Kordofan, and Sennar States, Sudan.

Schistosomiasis prevalence has remained high in some areas due to reinfection despite repeated mass drug administration interventions. We aimed to explore its risk factors in order to help to design adequate interventions in such high-transmission areas. A total of 6225 individuals residing in 60 villages in 8 districts of North Kordofan, Blue Nile, or Sennar States, Sudan participated in the community-based survey in March 2018. First, we investigated Schistosoma haematobium and Schistosoma mansoni prevalences among school-aged children and adults. Second, the associations between risk factors and schistosomiasis were explored. Those without any type of latrine in their households had higher odds of being infected with schistosomiasis than those with a latrine (odds ratio (OR) = 1.53; 95% confidence interval (CI) 1.20-1.94; p = 0.001), and the odds of being positive for schistosomiasis among people living in a household without an improved latrine were higher than for their counterparts with an improved latrine (OR = 1.63; CI 1.05-2.55; p = 0.03). Furthermore, people with households or outside compounds found to contain human faeces had higher odds of being infected with schistosomiasis than their counterparts (OR = 1.36, 95% CI 1.01-1.83, p = 0.04). Installing an improved latrine and eliminating open defecation should be highlighted in schistosomiasis elimination projects in high-transmission areas.

Tctp, a unique Ing5-binding partner, inhibits the chromatin binding of Enok in Drosophila.

The MOZ/MORF histone acetyltransferase complex is highly conserved in eukaryotes and controls transcription, development, and tumorigenesis. However, little is known about how its chromatin localization is regulated. Inhibitor of growth 5 (ING5) tumor suppressor is a subunit of the MOZ/MORF complex. Nevertheless, the in vivo function of ING5 remains unclear. Here, we report an antagonistic interaction between Drosophila Translationally controlled tumor protein (TCTP) (Tctp) and ING5 (Ing5) required for chromatin localization of the MOZ/MORF (Enok) complex and H3K23 acetylation. Yeast two-hybrid screening using Tctp identified Ing5 as a unique binding partner. In vivo, Ing5 controlled differentiation and down-regulated epidermal growth factor receptor signaling, whereas it is required in the Yorkie (Yki) pathway to determine organ size. Ing5 and Enok mutants promoted tumor-like tissue overgrowth when combined with uncontrolled Yki activity. Tctp depletion rescued the abnormal phenotypes of the Ing5 mutation and increased the nuclear translocation of Ing5 and chromatin binding of Enok. Nonfunctional Enok promoted the nuclear translocation of Ing5 by reducing Tctp, indicating a feedback mechanism between Tctp, Ing5, and Enok to regulate histone acetylation. Therefore, Tctp is essential for H3K23 acetylation by controlling the nuclear translocation of Ing5 and chromatin localization of Enok, providing insights into the roles of human TCTP and ING5-MOZ/MORF in tumorigenesis.

Citation Activity of Journal of Korean Medical Science in 2011-2020: Reflection on the Most and Least Cited Items.

BACKGROUND: The Journal of Korean Medical Science (JKMS) is a weekly periodical published by the Korean Academy of Medical Sciences. JKMS invites global researchers to submit articles covering various areas in general medicine. The present article's aim was to analyze citations of JKMS articles in 2011-2020 for updating editorial policies. METHODS: Citation records of JKMS articles were tracked in Web of Science (WoS), Clarivate® from August 2021 to June 2022. RESULTS: In 2011-2020, JKMS published 2,880 articles, including 2,757 (96.0%) ever cited. All reviews (57/57) and 96% of original research reports (2,184 out of 2,264) received at least one citation. Brief communications, opinions, and images were least cited items. Of 36 subject categories covered by JKMS, only biomedical engineering was significantly less advantageous citation-wise. Five articles published in 2012-2017 attracted more than 100 citations. Most other articles were cited less than 50 times. Article categories of nationwide epidemiology, disease or patient registries, clinical trials, and infectious diseases were distinguished as well cited. Of 378 articles published in 2020, 10 were cited at least 100 times; all these ten items were related to severe acute respiratory syndrome coronavirus 2 and coronavirus disease 2019. In the past 5 years, studies on health care laws, management, and some specific topics in clinical specialties were not cited. The citation trends in WoS, Crossref, and Scopus were similar while PubMed Central records were roughly twice less. CONCLUSION: Most of JKMS articles are cited during 5 years post publication, with 1.4% non-citation rate. The obtained results suggest that inviting review articles in clinical sciences, research reports on hot medical topics, and nationwide database analyses may attract more author interest and related citations.

Black Ginseng Extract Suppresses Airway Inflammation Induced by Cigarette Smoke and Lipopolysaccharides In Vivo.

Cigarette smoke (CS) is a risk factor that can induce airway enlargement, airway obstruction, and airway mucus hypersecretion. Although studies have shown that Korean black ginseng extract (BGE) has potent anti-inflammatory and antioxidant activities, the CS-induced inflammatory responses and molecular mechanisms are yet to be examined. The aim of this study was to examine the effect of BGE on the airway inflammatory response and its molecular mechanisms, using CS/lipopolysaccharides (LPS)-exposed animals and PMA-stimulated human airway epithelial NCI-H292 cells. The results show that BGE inhibited the recruitment of immune cells and the release of inflammatory mediators, such as tumor necrosis factor (TNF)-α and interleukin (IL)-6, monocyte chemoattractant protein (MCP)-1, elastase, and reactive oxygen species (ROS) in the airways of CS/LPS-exposed animals. BGE inhibited mucus secretion and the expression of Mucin 5AC (MUC5AC). Furthermore, BGE exhibited an anti-inflammatory effect by downregulating a signaling pathway mediated by transforming growth factor-ß-activated kinase (TAK) 1, an important protein that accelerates inflammation by cigarette smoke (CS). Overall, the findings show that BGE inhibits lung inflammation and mucus secretion by decreasing the activation of TAK1 both in human epithelial cells and in CS/LPS-exposed animals, and could be a potential adjuvant in the treatment and prevention of airway inflammatory diseases caused by airway irritants such as CS.

Association Between the Prevalence of Schistosomiasis in Elementary School Students and Their Parental Occupation in Sudan.

Global efforts to identify groups at high risk for schistosomiasis have mainly concentrated on identifying their geographical distribution. Investigations on the socioeconomic characteristics of high-risk groups are relatively scarce. This study aimed to explore the associations between schistosomiasis among students and their parents' occupations. A nationwide cross-sectional survey was conducted targeting 105,167 students in 1,772 primary schools across Sudan in 2017. From these students, 100,726 urine and 96,634 stool samples were collected to test for Schistosoma haematobium and S. mansoni infection. A multi-level mixed effect analysis was used with age and sex as fixed factors, and school as a random factor. The odd ratios (ORs) of practicing open defecation among farmers' children were almost 5 times higher than their counterparts whose parents were government officials (OR=4.97, 95% confidence intervals (CIs): 4.57-5.42, P<0.001). The ORs of contacting water bodies for watering livestock among farmers' children were more than 4 times higher than those of children whose parents were government officials (OR=4.59, 95% CIs: 4.02-5.24, P<0.001). This study shows that schistosomiasis represents a disease of poverty and that farmers' children constituted a high-risk group.

Daphnodorin C isolated from the stems of Daphne kiusiana Miquel attenuates airway inflammation in a mouse model of chronic obstructive pulmonary disease.

BACKGROUND: Since long-term or high-dose use of COPD medication causes adverse effects in patients with COPD, more effective and safer ways to manage COPD symptoms are required. Daphne kiusiana Miquel is a medicinal plant, but its anti-COPD efficacy was little studied. PURPOSE: We investigated the anti-COPD activity and molecular mechanism of action of active compounds isolated from D. kiusiana to find drug candidates for COPD. METHODS: We isolated seven compounds (1-7) in an ethyl acetate (EtOAc) fraction from D. kiusiana, and determined that seven compounds effectively control the inflammatory responsiveness in both PMA-stimulated lung epithelial cells (in vitro) and/or in COPD model mice using cigarette smoke- and lipopolysaccharides-exposed animals in vivo. RESULTS: We show that the ethyl acetate (EtOAc) fraction from D. kiusiana. suppresses inflammatory response in both PMA-stimulated human lung epithelial cells (in vitro) and COPD model mice (in vivo). The EtOAc fraction effectively suppresses various inflammatory responses, such as mucus secretion, ROS production, bronchial recruitment of inflammatory cells, and release of proinflammatory cytokines. Additionally, we isolated three compounds with anti-inflammatory efficacy from the EtOAc fraction, out of which daphnodorin C was the most effective. Finally, we demonstrated that daphnodorin C negatively regulates inflammatory gene expression by suppressing NF-κB and specific MAPK signaling pathways (JNK and p38) in vitro and in vivo. CONCLUSIONS: These results suggest that daphnodorin C could be a promising therapeutic alternative for managing COPD symptoms.

Analysis of PubMed and KoreaMed Indexed Korean Publications on COVID-19.

During the coronavirus disease 2019 (COVID-19) pandemic, publications on the disease have exploded globally. The present study analyzed PubMed and KoreaMed indexed COVID-19 publications by Korean researchers from January 1, 2020 to August 19, 2021. A total of 83,549 COVID-19 articles were recorded in PubMed and 1,875 of these were published by Korean authors in 673 journals (67 Korean and 606 overseas journals). The KoreaMed platform covered 766 articles on COVID-19, including 612 by Korean authors. Among the Journal of Korean Medical Science (JKMS) articles on COVID-19, PubMed covered 176 and KoreaMed 141 documents. Korean researchers contributed to 2.2% of global publications on COVID-19 in PubMed. The JKMS has published most articles on COVID-19 in Korea.

Transmission Dynamics of Schistosoma haematobium among School-Aged Children: A Cohort Study on Prevalence, Reinfection and Incidence after Mass Drug Administration in the White Nile State of Sudan.

The reinfection rate of schistosomiasis after mass drug administration (MDA) has not been documented in Sudan. We aimed to explore the transmission dynamics of urogenital schistosomiasis after MDA, targeting school-aged children in the White Nile State of Sudan, assessing the prevalence, reinfection rate, and incidence. A single dose of praziquantel (40 mg/kg) was administered to 1951 students in five primary schools from January to February 2018 immediately after a baseline survey, and follow-up surveys were performed at 2 weeks and 6 months after treatment. We examined Schistosoma haematobium eggs by centrifugation methods. The overall reinfection rate at 6 months after treatment was 9.8% (95% confidence interval: 0.5-17.4%). By school, the reinfection rate was highest in the Al Hidaib school, whose prevalence was highest at baseline. The reinfection rate was significantly higher in high-infection areas than low-infection areas (p = 0.02). Of the prevalence at 6 months in high-infection areas, 41% of cases were due to reinfection. MDA interventions are decided upon and undertaken at the district level. A more targeted treatment strategy should be developed with a particular focus on tracking high-risk groups, even within a school or a community.