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.

Molecular Confirmation of Taenia solium Taeniasis in Child, Timor-Leste.

We report a case of Taenia solium taeniasis in a 10-year-old child in Timor-Leste, confirmed by molecular analysis, suggesting T. solium transmission to humans is occurring in Timor-Leste. Proactive measures are needed to improve public understanding of prevalence, geographic spread, and health implications of human taeniasis and cysticercosis in Timor-Leste.

Regulation of epithelial integrity and organ growth by Tctp and Coracle in Drosophila.

Regulation of cell junctions is crucial for the integrity of epithelial tissues and organs. Cell junctions also play roles in controlling cell proliferation for organ growth. Translationally controlled tumor protein (TCTP) is a conserved protein involved in growth control, but its role in cell junctions is unknown. Here we show that Drosophila Tctp directly interacts with the septate junction protein Coracle (Cora) to regulate epithelial integrity and organ growth. Tctp localizes together with Cora in the epidermis of the embryo. Loss of Cora reduces the level of Tctp in the epidermis but not vice versa. cora/+ or Tctp/+ single heterozygotes develop normally to adulthood. However, double heterozygotes for cora and Tctp mutations show severe disruption of epithelia causing synthetic lethality in the embryo. Double knockdown of Cora and Tctp in eye imaginal disc synergistically leads to disruption of the eye disc, resulting in a severe reduction or loss of eye and head. Conversely, double knockdown of Cora and Tctp in wing disc causes overgrowth as well as cell death. Inhibition of cell death under this condition causes hyperplastic growth of the wing disc. Tctp also shows direct and functional interaction with Cora-associated factors like Yurt and Na+/K+-ATPase. This study suggests that proper levels of Tctp and Cora are essential for the maintenance of the Cora complex and the integrity of epithelia. Our data also provide evidence that both Cora and Tctp are required to suppress overgrowth in developing wing.

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.

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.

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.

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.

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.

Prevalence and Risk Factors of Intestinal Helminthiasis in Remote Mountainous Villages of Northern Lao PDR: A Cross-Sectional Study.

Helminth infections are prevalent in Lao People's Democratic Republic (Lao PDR). This study aimed at determining the prevalence and risk factors of intestinal helminthiasis in remote mountainous villages of northern Lao PDR. During the dry season in January 2017, a cross-sectional survey was conducted in 3 remote mountainous villages in Oudomxay province, Lao PDR. Villagers older than 18 years of age who agreed to submit stool samples or undergo an interview, were recruited. Stool samples from 198 individuals were examined by the Kato-Katz method, and a questionnaire surveyed 161 individuals among them. Univariable and multivariable logistic regression analyses were used to identify risk factors associated with the intestinal helminthiasis. An overall prevalence of intestinal helminthiasis was 75.8%. Hookworm infection was the most common (63.1%), followed by Opisthorchis viverrini/minute intestinal flukes (17.7%), Taenia spp. (15.2%), Trichuris trichiura (2.0%), Ascaris lumbricoides (1.5%), and Enterobius vermicularis (1.0%). Questionnaire analysis revealed sex (male) and absence of latrine to be significant risk factors for hookworm infection and consumption of raw meat for taeniasis. These results suggest that the mountainous area in northern Lao PDR has a different composition of helminth infections from other studies conducted in Lao PDR; a high prevalence of hookworm infection and taeniasis and low prevalence of T. trichiura and A. lumbricoides infections were observed. Also, liver flukes or intestinal flukes were similarly prevalent in the mountainous area.

Longifolioside A inhibits TLR4-mediated inflammatory responses by blocking PKCδ activation in LPS-stimulated THP-1 macrophages.

Longifolioside A is an iridoid glucoside compound isolated from Pseudolysimachion rotundum var. subintegrum, which has been used in traditional herbal medicines to treat respiratory inflammatory diseases. Logifolioside A is a potent antioxidant; however, its underlying pharmacological mechanisms of action in inflammatory diseases are unknown. Here, we investigated the inhibitory effects of longifolioside A in lipopolysaccharide (LPS)-stimulated toll-like receptor 4 (TLR4) signal transduction systems using human THP-1 macrophages and HEK293 cells stably expressing human TLR4 protein (293/HA-hTLR4). Longifolioside A significantly reduced the release of inflammatory cytokines such as interleukin (IL)-6, -8, and tumor necrosis factor (TNF)-α in LPS-stimulated THP-1 macrophages. Furthermore, longifolioside A inhibited the expression of inflammatory mediator genes such as inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 that produce nitric oxide (NO) and prostaglandin E2 (PGE2), respectively. Longifolioside A suppressed the phosphorylation of PKCδ, IRAK4, IKKα/ß, IκBα, and mitogen-activated protein (MAP) kinases (ERK 1/2 and JNK, but not p38), thereby inactivating the nuclear localization of NF-κB and AP-1, and thus decreasing the expression of inflammatory response genes. Notably, longifolioside A disrupted the interaction between human TLR4 and the TIR domain-containing adaptor protein (TIRAP), an early step during TLR4 activation, thereby reducing IL-8 secretion in 293/HA-hTLR4 cells. This inhibitory effect was comparable to that of TAK-242 (a TLR4 inhibitor, or resatorvid). Our results indicate that longifolioside A prevents inflammatory response by suppressing TLR4 activation required for NF-κB and AP-1 activation.

Status of Editing and Publishing of Scholarly Journals by Academic Societies of Science and Technology in Korea.

BACKGROUND: The present study analyzed publishing data of scholarly journals which were published in 2018 by academic societies of science and technology in Korea to observe journal editing and publishing status. METHODS: A total of 346 regional journals (59 natural science, 118 engineering, 44 agriculture, fisheries, and oceanography, and 125 medical and pharmacy) and 141 international journals (32 natural science, 43 engineering, 12 agriculture, fisheries, and oceanography, 54 medical and pharmacy) were included in this analysis, which applied the journal review by the Korea Federation of Science and Technology. Websites of the journals and the submitted publication data in 2019 were reviewed. RESULTS: Except for a few journals, all of the journals were published by academic societies. Basic information of journals was well displayed by both offline and online. Most of the 346 regional journals were published in Korean language or mixed with English but 77 (22.3%), mostly medical, were in English. One-third (n = 104) journals published less than 40 articles while 9 published over 200, and 261 journals (75.4%) received less than 100 submissions in 2018. Most (n = 298, 86.1%) of them were enlisted in the Korean Citation Index (KCI). Editorial board members performed manuscript editing in 171 (49.4%) journals, and most of the journals paid < 50,000,000 won for publishing costs. Of 141 international journals, 138 (97.9%) were published in English and all of them published overseas submissions. Forty-one (29.1%) journals accepted < 20% of submissions but 58 (41.1%) accepted 100%. Of them, 124 (87.9%) were indexed in the KCI, 93 (66.0%) in the Web of Science, 120 in Scopus, and 62 in PubMed. Editorial board members in 38 (27.0%) journals took responsibility of manuscript editing. Publishing cost of 79 (56.0%) journals was < 50,000,000 won. Only 157 (32.2%) of total 487 journals, mostly medical, documented gendered innovation in their instruction to authors. CONCLUSION: Most of the Korean science and technology journals keep global standard of editing and publishing. Their offline and online visibility is acceptable but most regional journals are small and of low academic impact while international journals are globally indexed and acknowledged. Korean scholarly journals should invite more and better articles to keep quality publication.

Parasitological Observation in Schoolchildren with Urogenital Schistosomiasis Following Treatment with Three Different Brands of Praziquantel.

This study compared the anthelminthic effects of three different brands of praziquantel being used in Sudan against Schistosoma haematobium (S. haematobium) infection. We enrolled 1,286 schoolchildren from six primary schools and examined their urine samples for eggs of S. haematobium at the baseline survey and follow-up two weeks after administering the medication. The schoolchildren were divided into three groups based on the three brands of praziquantel (different material production), with two school children for one brand. The overall baseline prevalence of S. haematobium infection was 15.5%. Two weeks after treatment with brands A, B, and C of praziquantel, cure rates were 87.1%, 82.4% and 83.8% respectively, and the egg-reduction rates were 69.0%, 81.0% and 70.6% respectively. There was no statistically significant difference in cure rates and egg-reduction rates between the three brands. We conclude that the three different commercial brands of praziquantel used in Sudan have similar anthelminthic effects on S. haematobium.

Comparison of the Change in the Prevalence and Intensity of Schistosoma haematobium Infection Between High and Low Prevalence Areas of White Nile State, Sudan.

This study aimed to investigate whether mass drug administration (MDA) intervention has an equivalent effect on reducing the prevalence and intensity of Schistosoma haematobium infection regardless of the baseline values. A repeated cross-sectional survey was performed targeting students of 12 primary schools in Al Jabalain and El Salam districts of White Nile State, Sudan, at both 1 week before and 8 months after the MDA. Prior to the baseline survey, school-aged children in Al Jabalain had received MDA interventions twice in 4 years, while those in El Salam had not. The baseline prevalence was 9.1% in Al Jabalain and 35.2% in El Salam, which were reduced to 1.8% and 5.5% at 8 months after the MDA, respectively. The corresponding reduction rates were 80.3% and 84.4%, not significant difference between both districts. However, changes in the geometric mean intensity (GMI) of egg counts were significantly different between both districts. The baseline GMIs were 14.5 eggs per 10 ml of urine (EP10) in Al Jabalain and 18.5 EP10 in El Salam, which were reduced to 7.1 and 11.2 EP10 after treatment, respectively. The corresponding reduction rates were 51.0% and 39.5%. In conclusion, MDA interventions were found to bring about similar relative reduction in prevalence regardless of the baseline value; however, the relative reduction in infection intensity was more salient in the district with a low baseline value for both prevalence and intensity. This clearly points to the importance of repeated MDA interventions in endemic areas, which will eventually contribute to schistosomiasis elimination.

Prevalence of Toxocariasis and Its Risk Factors in Patients with Eosinophilia in Korea.

Eosinophilia occurs commonly in many diseases including allergic diseases and helminthic infections. Toxocariasis has been suggested as one cause of eosinophilia. The present study was undertaken to examine the prevalence of toxocariasis in patients with eosinophilia and to identify the risk factors for toxocariasis. This prospective cohort study recruited a total of 81 patients with eosinophilia (34 males and 47 females) who visited the outpatient clinic at Seoul National University Hospital from January 2017 to February 2018 and agreed to participate in this study. The prevalence of toxocariasis was examined by T. canis-specific ELISA, and the various risk factors for toxocariasis were evaluated by a questionnaire survey. Among 81 patients with eosinophilia, 18 were positive for anti-T. canis antibodies (22.2%); 88.9% were male (16/18) and 11.1% were female (2/18). Multivariate statistical analysis revealed that males (OR 21.876, 95% CI: 1.667-287.144) with a history of consuming the raw meat or livers of animals (OR 5.899, 95% CI: 1.004-34.669) and a heavy alcohol-drinking habit (OR 8.767, 95% CI: 1.018-75.497) were at higher risk of toxocariasis in patients with eosinophilia. Toxocariasis should be considered a potential cause of eosinophilia when the patient has a history of eating the raw meat or livers of animals in Korea. A single course of albendazole is recommended to reduce the migration of Toxocara larvae in serologically positive cases with eosinophilia.

Epidemiological Survey on Schistosomiasis and Intestinal Helminthiasis among Village Residents of the Rural River Basin Area in White Nile State, Sudan.

There have been some reports on schistosomiasis of school children in Sudan's Nile River basin area; however, information about the infection status of Schistosoma species and intestinal helminths among village residents of this area is very limited. Urine and stool samples were collected from the 1,138 residents of the Al Hidaib and Khour Ajwal villages of White Nile State, Sudan in 2014. The prevalence of overall schistosomiasis and intestinal helminthiasis was 36.3% and 7.7%, respectively. Egg positive rates were 35.6% for Schistosoma haematobium, 2.6% for S. mansoni, and 1.4% were mixed. The prevalence of schistosomiasis was significantly higher in men (45.6%) than in women (32.0%), in Khou Ajwal villagers (39.4%) than in Al Hidaib villagers (19.2%), and for age groups ≤15 years old (51.5%) than for age groups >15 years old (13.2%). The average number of eggs per 10 ml urine (EP10) of S. haematobium infections was 18.9, with 22.2 eggs in men vs 17.0 in women and 20.4 in Khou Ajwal villagers vs 8.1 in Al Hidaib villagers. In addition to S. mansoni eggs, 4 different species of intestinal helminths were found in the stool, including Hymenolepis nana (6.6%) and H. diminuta (1.0%). Collectively, urinary schistosomiasis is still prevalent among village residents in Sudan's White Nile River basin and was especially high in men, children ≤15 years, and in the village without a clean water system. H. nana was the most frequently detected intestinal helminths in the 2 villages.

Fisetin inhibits TNF-α/NF-κB-induced IL-8 expression by targeting PKCδ in human airway epithelial cells.

Fisetin (3,7,3',4'-tetrahydroxyflavone), a natural flavonoid, is a therapeutic agent for respiratory inflammatory diseases such as chronic obstructive pulmonary disease (COPD). However, detailed molecular mechanisms regarding the target protein of fisetin remain unknown. Fisetin significantly reduces tumour necrosis factor alpha (TNF-α)-induced interleukin (IL)-8 levels by inhibiting both nuclear factor kappa B (NF-κB) transcriptional activity and the phosphorylation of its upstream effectors. We show that fisetin prevents interactions between protein kinase C (PKC)δ and TNF receptor-associated factor 2 (TRAF2), thereby inhibiting the inhibitor of kappa B kinase (IKK)/NF-κB downstream signalling cascade. Furthermore, we found that fisetin directly binds to PKCδ in vitro. Our findings provide evidence that fisetin inhibits the TNF-α-activated IKK/NF-κB cascade by targeting PKCδ, thereby mediating inflammatory diseases such as COPD. These data suggest that fisetin is a good therapeutic drug for the treatment of inflammatory lung diseases, such as COPD, by inhibiting the TNF-α/NF-κB signalling pathway.