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Abstract Background Stress is an important cause of skin disease, including hair loss. The hormonal response to stress is due to the HPA axis, which comprises hormones such as corticotropin releasing factor (CRF), adrenocorticotropic hormone (ACTH), and cortisol. Many reports have shown that CRF, a crucial stress hormone, inhibits hair growth and induces hair loss. However, the underlying mechanisms are still unclear. The aim of this study was to examine the effect of CRF on human dermal papilla cells (DPCs) as well as hair follicles and to investigate whether the HPA axis was established in cultured human DPCs. Results CRF inhibited hair shaft elongation and induced early catagen transition in human hair follicles. Hair follicle cells, both human DPCs and human ORSCs, expressed CRF and its receptors and responded to CRF. CRF inhibited the proliferation of human DPCs through cell cycle arrest at G2/M phase and induced the accumulation of reactive oxygen species (ROS). Anagen-related cytokine levels were downregulated in CRF-treated human DPCs. Interestingly, increases in proopiomelanocortin (POMC), ACTH, and cortisol were induced by CRF in human DPCs, and antagonists for the CRF receptor blocked the effects of this hormone. Conclusion The results of this study showed that stress can cause hair loss by acting through stress hormones. Additionally, these results suggested that a fully functional HPA axis exists in human DPCs and that CRF directly affects human DPCs as well as human hair follicles under stress conditions.

Background General anesthesia is inevitable for pediatric patients undergoing surgery, though volatile anesthetic agents may cause neuroinflammation and neurodevelopmental impairment; however, the underlying pathophysiology remains unclear. We aimed to investigate the neuroinflammation mechanism in developing rat brains associated with sevoflurane exposure time, by identifying the specific damage-associated molecular patterns (DAMPs) pathway and evaluating the effects of non-steroidal anti-inflammatory drugs (NSAIDs) in alleviating neuroinflammation. Methods A three-step experiment was conducted to investigate neuroinflammation induced by sevoflurane. First, the exposure time required for sevoflurane to cause neuroinflammation was determined. Next, the specific pathways of DAMPs involved in neuroinflammation by sevoflurane were identified. Finally, the effects of NSAIDs on sevoflurane-induced neuroinflammation were investigated. The expression of various molecules in the rat brain were assessed using immunohistochemistry, immunofluorescence, quantitative real-time polymerase chain reaction, western blot analysis, and enzyme-linked immunosorbent assay. Results In total, 112 rats (aged 7 days) were used, of which six rats expired during the experiment (mortality rate, 5.3%). Expression of CD68, HMGB-1, galectin-3, TLR4, TLR9, and phosphorylated NF-κB was significantly increased upon 6 h of sevoflurane exposure. Conversely, transcriptional levels of TNF-α and IL-6 significantly increased and IFN-γ significantly decreased after 6 h of sevoflurane exposure. Co-administration of NSAIDs with sevoflurane anesthesia significantly attenuated TNF-α and IL-6 levels and restored IFN-γ levels. Conclusions In conclusion, 6 h of sevoflurane exposure induces neuroinflammation through the DAMPs pathway, HMGB-1, and galectin-3. Co-administration of ibuprofen reduced sevoflurane-induced neuroinflammation.

Background Previous studies have reported that oxidative stress contributes to obesity characterized by adipocyte hypertrophy. However, mechanism has not been studied extensively. In the current study, we evaluated role of extracellular vimentin secreted by oxidized low-density lipoprotein (oxLDL) in energy metabolism in adipocytes. Methods We treated 3T3-L1-derived adipocytes with oxLDL and measured vimentin which was secreted in the media. We evaluated changes in uptake of glucose and free fatty acid, expression of molecules functioning in energy metabolism, synthesis of adenosine triphosphate (ATP) and lactate, markers for endoplasmic reticulum (ER) stress and autophagy in adipocytes treated with recombinant vimentin. Results Adipocytes secreted vimentin in response to oxLDL. Microscopic evaluation revealed that vimentin treatment induced increase in adipocyte size and increase in sizes of intracellular lipid droplets with increased intracellular triglyceride. Adipocytes treated with vimentin showed increased uptake of glucose and free fatty acid with increased expression of plasma membrane glucose transporter type 1 (GLUT1), GLUT4, and CD36. Vimentin treatment increased transcription of GLUT1 and hypoxia-inducible factor 1α (Hif-1α) but decreased GLUT4 transcription. Adipose triglyceride lipase (ATGL), peroxisome proliferator-activated receptor γ (PPARγ), sterol regulatory element-binding protein 1 (SREBP1), diacylglycerol O-acyltransferase 1 (DGAT1) and 2 were decreased by vimentin treatment. Markers for ER stress were increased and autophagy was impaired in vimentin-treated adipocytes. No change was observed in synthesis of ATP and lactate in the adipocytes treated with vimentin. Conclusion We concluded that extracellular vimentin regulates expression of molecules in energy metabolism and promotes adipocyte hypertrophy. Our results show that vimentin functions in the interplay between oxidative stress and metabolism, suggesting a mechanism by which adipocyte hypertrophy is induced in oxidative stress.

Summary: Background: Disease susceptibility and progression of Mycobacterium avium complex pulmonary disease (MAC-PD) is associated with multiple factors, including low body mass index (BMI). However, the specific impact of low BMI on MAC-PD progression remains poorly understood. This study aims to examine the progression of MAC-PD in the context of low BMI, utilising a disease-resistant mouse model. Methods: We employed a MAC infection-resistant female A/J mouse model to compare the progression of MAC-PD under two dietary conditions: one group was fed a standard protein diet, representing protein-energy unrestricted conditions, and the other was fed a low protein diet (LPD), representing protein-energy restriction. Findings: Our results reveal that protein-energy restriction significantly exacerbates MAC-PD progression by disrupting lipid metabolism. Mice fed an LPD showed elevated fatty acid levels and related gene expressions in lung tissues, similar to findings of increased fatty acids in the serum of patients who exhibited the MAC-PD progression. These mice also exhibited increased CD36 expression and lipid accumulation in macrophages upon MAC infection. In vitro experiments emphasised the crucial role of CD36-mediated palmitic acid uptake in bacterial proliferation. Importantly, in vivo studies demonstrated that administering anti-CD36 antibody to LPD-fed A/J mice reduced macrophage lipid accumulation and impeded bacterial growth, resulting in remarkable slowing disease progression. Interpretation: Our findings indicate that the metabolic status of host immune cells critically influences MAC-PD progression. This study highlights the potential of adequate nutrient intake in preventing MAC-PD progression, suggesting that targeting CD36-mediated pathways might be a host-directed therapeutic strategy to managing MAC infection. Funding: This research was funded by the National Research Foundation of Korea, the Korea Research Institute of Bioscience and Biotechnology, and the Korea National Institute of Health.

Background Robust risk assessment is crucial for the growing repaired tetralogy of Fallot population at risk of major adverse clinical outcomes; however, current tools are hindered by lack of validation. This study aims to develop and validate a risk prediction model for death in the repaired tetralogy of Fallot population. Methods and Results Patients with repaired tetralogy of Fallot enrolled in the INDICATOR (International Multicenter Tetralogy of Fallot Registry) cohort with clinical, arrhythmia, cardiac magnetic resonance, and outcome data were included. Patients from London, Amsterdam, and Boston sites were placed in the development cohort; patients from the Toronto site were used for external validation. Multivariable Cox regression was used to evaluate factors associated with time from cardiac magnetic resonance until the primary outcome: all‐cause death. Of 1552 eligible patients (n=1221 in development, n=331 in validation; median age at cardiac magnetic resonance 23.4 [interquartile range, 15.6–35.6] years; median follow up 9.5 years), 102 (6.6%) experienced the primary outcome. The multivariable Cox model performed similarly during development (concordance index, 0.83 [95% CI, 0.78–0.88]) and external validation (concordance index, 0.80 [95% CI, 0.71–0.90]) and identified older age at cardiac magnetic resonance, obesity, type of tetralogy of Fallot repair, higher right ventricular end‐systolic volume index, and lower biventricular global function index as independent predictors of death. A risk‐scoring algorithm dividing patients into low‐risk (score ≤4) versus high‐risk (score >4) groups was validated to effectively discriminate risk of death (15‐year survival of 95% versus 74%, respectively; P

Abstract Background Krüppel-like factor 10 (KLF10) is involved in a positive feedback loop that regulates transforming growth factor β (TGFβ) signaling, and TGFβ plays an important role in the pathogenesis of liver disease. Here, we investigated whether KLF10 deletion affects the development of liver fibrosis and hepatocellular carcinoma (HCC). Methods We induced KLF10 deletion in C57BL/6 mice. Liver fibrosis was induced by feeding a diet high in fat and sucrose (high-fat diet [HFD]), whereas HCC was produced by intraperitoneal administration of N-diethylnitrosamine (DEN). An in vitro experiment was performed to evaluate the role of KLF10 in the cancer microenvironment using Hep3B and LX2 cells. An immunohistochemical study of KLF10 expression was performed using human HCC samples from 60 patients who had undergone liver resection. Results KLF10 deletion resulted in an increased DEN-induced HCC burden with significant upregulation of SMAD2, although loss of KLF10 did not alter HFD-induced liver fibrosis. DEN-treated mice with KLF10 deletion exhibited increased levels of mesenchymal markers (N-cadherin and SNAI2) and tumor metastasis markers (matrix metalloproteinases 2 and 9). KLF10 depletion in Hep3B and LX2 cells using siRNA was associated with increased invasiveness. Compared with co-culture of KLF10-preserved Hep3B cells and KLF10-intact LX2 cells, co-culture of KLF10-preserved Hep3B cells and KLF10-depleted LX2 cells resulted in significantly enhanced invasion. Low KLF10 expression in resected human HCC specimens was associated with poor survival. Conclusion The results of this study suggest that loss of KLF10 facilitates liver cancer development with alteration in TGFβ signaling.

Abstract Complement-dependent cytotoxicity (CDC), which eliminates aberrant target cells through the assembly and complex formation of serum complement molecules, is one of the major effector functions of anticancer therapeutic antibodies. In this study, we discovered that breaking the symmetry of natural immunoglobulin G (IgG) antibodies significantly increased the CDC activity of anti-CD20 antibodies. In addition, the expression of CD55 (a checkpoint inhibitor in the CDC cascade) was significantly increased in a rituximab-resistant cell line generated in-house, suggesting that CD55 overexpression might be a mechanism by which cancer cells acquire rituximab resistance. Based on these findings, we developed an asymmetric bispecific antibody (SBU-CD55 × CD20) that simultaneously targets both CD55 and CD20 to effectively eliminate rituximab-resistant cancer cells. In various cancer cell lines, including rituximab-resistant lymphoma cells, the SBU-CD55 × CD20 antibody showed significantly higher CDC activity than either anti-CD20 IgG antibody alone or a combination of anti-CD20 IgG antibody and anti-CD55 IgG antibody. Furthermore, the asymmetric bispecific antibody (SBU-CD55 × CD20) exhibited significantly higher CDC activity against rituximab-resistant cancer cells compared to other bispecific antibodies with symmetric features. These results demonstrate that enhancing CDC with an asymmetric CD55-binding bispecific antibody could be a new strategy for developing therapeutics to treat patients with relapsed or refractory cancers.

Newborn incompetence of the sphincter of Oddi is rare. While there are many causes of reflux of air or ingested contrast material into the biliary tree in adults, in the newborn, it is usually due to incompetence of the sphincter of Oddi associated with partial or complete duodenal obstruction. This paper presents upper gastrointestinal series findings of incompetence of the sphincter of Oddi associated with duodenal stenosis in a 3-day-old newborn. If pneumobilia is identified in the newborn, although the possibility is low, clinicians should consider incompetence of the sphincter of Oddi with duodenal obstruction as well as portal vein gas.

PURPOSE This study aims to provide empirical foundational data for the development of a new profit model in Korean professional baseball. It does so by examining the influence of professional baseball NFT product attributes on customer perceptions of value, satisfaction, and purchase intention. METHODS Data were collected from consumers who have experience purchasing KBOLLECT. A total of 363 samples were collected for analysis. Surveys were utilized for data collection, encompassing 39 items that measured product characteristics, perceived value, satisfaction, purchase intention, and demographic information. Using the collected data, various statistical analyses were conducted including descriptive statistics, exploratory factor analysis, reliability analysis, correlation analysis and multiple regression using SPSS version 21. The ensuing results from the correlation analysis and multiple regression analysis are as follows. RESULTS Product features, including aesthetics, symbolism, and scarcity, had a positive impact on consumer’s perceived emotional value. Moreover, product features, encompassing aesthetics, symbolism, scarcity, and creativity played a significant role in enhancing consumer’s perceived economic value. Furthermore, product attributes such as aesthetics, symbolism, and creativity positively contributed to consumer’s perceived social value. Similarly, product features comprising aesthetics, scarcity, creativity, and symbolism positively affected consumer’s perceived intellectual value. Additionally, the research revealed that product features related to aesthetics, symbolism, creativity, and scarcity were instrumental in bolstering consumer. Importantly, these very attributes, including aesthetics, symbolism, scarcity, and creativity, exhibited a positive influence on consumers’ purchase intentions. CONCLUSIONS In conclusion, this study underscores the substantial impact of professional baseball NFT product characteristics on consumers’ perceptions, satisfaction, and purchase intentions. To maintain enduring relationships with consumers who engage with professional baseball NFT products, it is essential to fortify these product attributes and offer diverse services utilizing them.

The development of new functional foods that can potentially reduce the risk of diseases, such as osteoporosis, has received increasing attention in recent years. Here we demonstrated that silk sericin-based functional food (SSBF) exerted preventive and therapeutic effects against bone loss. Sericin isolated at 70 °C for 60 min from the cocoon of Bombyx mori stimulated osteoblast differentiation by increasing osteoblastic gene expression while inhibiting receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation in vitro. Micro-computed tomography analysis revealed that pre- and post-oral administration of SSBF increased bone mass in ovariectomized mouse model in vivo. Furthermore, dynamic bone histomorphometry analysis revealed that SSBF enhanced osteoblast activity and suppressed bone resorption by reducing the number of osteoclasts. These findings indicated the potential role of SSBF in preventing and being a therapeutic candidate for osteoporosis.

Objectives The Korea Disease Control and Prevention Agency promotes vaccination by regularly providing information on its benefits for reducing the severity of coronavirus disease 2019 (COVID-19). This study aimed to analyze the number of averted severe COVID-19 cases and COVID-19-related deaths by age group and quantify the impact of Republic of Korea’s nationwide vaccination campaign. Methods We analyzed an integrated database from the beginning of the vaccination campaign on February 26, 2021 to October 15, 2022. We estimated the cumulative number of severe cases and COVID-19-related deaths over time by comparing observed and estimated cases among unvaccinated and vaccinated groups using statistical modeling. We compared daily age-adjusted rates of severe cases and deaths in the unvaccinated group to those in the vaccinated group and calculated the susceptible population and proportion of vaccinated people by age. Results There were 23,793 severe cases and 25,441 deaths related to COVID-19. We estimated that 119,579 (95% confidence interval [CI], 118,901–120,257) severe COVID-19 cases and 137,636 (95% CI, 136,909–138,363) COVID-19-related deaths would have occurred if vaccination had not been performed. Therefore, 95,786 (95% CI, 94,659–96,913) severe cases and 112,195 (95% CI, 110,870–113,520) deaths were prevented as a result of the vaccination campaign. Conclusion We found that, if the nationwide COVID-19 vaccination campaign had not been implemented, the number of severe cases and deaths would have been at least 4 times higher. These findings suggest that Republic of Korea’s nationwide vaccination campaign reduced the number of severe cases and COVID-19 deaths.

The accessory tendon of the extensor hallucis longus is a common type of extensor hallucis longus variation. This is a case of a 38-year-old female patient who initially considered conservative treatment for a suspected partial rupture, but finally underwent surgery after being diagnosed with a complete rupture of the main tendon and accessory tendon medial to the main tendon on MRI scan.

Rice bodies are commonly detected in adults with rheumatoid arthritis and rarely occur in children. An 11-year-old female adolescent who visited our hospital for evaluation of knee pain underwent a MRI scan, which revealed an intra-articular mass. Arthroscopic examination of the mass confirmed conglomerated rice bodies. We report a case of rice bodies that clinically presented as intra-articular masses.

In general, neuroendocrine cancer develops in the digestive or respiratory tract, and when it is found in other organs, it is often due to metastasis. Primary neuroendocrine carcinoma of the breast occurs very rarely, and the exact clinical picture, radiological findings, treatment and prognosis are not well known. Furthermore, only a small number of literature reports have been published. Here, we report the imaging findings of primary neuroendocrine carcinoma in the breast of a 51-year-old female, along with a literature review.

Nuclear portein in testis (NUT) midline carcinoma is a very rare and low-differentiating malignant epithelial tumor that differentiates very aggressively and has poor prognosis. NUT midline carcinoma occurring in the lungs in particular can be confused with other cancers because few cases have been reported in Korea to date and can show various histological forms. Reports of radiology findings are very rare worldwide. Here we report the imaging findings of pulmonary NUT midline carcinoma in a 25-year-old female along with pathological findings.

PURPOSE The purpose of this study was to understand the current market trend for golf apparel rental services and to present basic data to revitalize the golf apparel rental service market and prepare continuous growth plans. METHODS The following keywords were selected for data collection: "golf wear + rental (렌탈)," "golf wear + rental (대여)," "golf apparel + rental (렌탈)," and "golf apparel + rental (대여).“ The analysis period was limited to two years and seven months from January 1, 2020 to July 31, 2022, when COVID-19 began. The analysis was focused on the top 60 keywords to simplify the network. RESULTS Various keywords were extracted through text mining, TF-IDF, connection centrality, emotional analysis, and semantic network analysis of big data analysis. These were then categorized into four factors: “golf apparel rental service,” “self-expression and authentication,” “sharing economy,” and “emotion.” CONCLUSIONS The results of this study show that young golfers are unreluctant and are generally positive in renting golf apparel. Therefore, if the growing paradigm of the consumption behavior of MZ-generation golfers is recognized and analyzed and the requirements are continuously satisfied through various strategies, there will be a higher possibility to help expand the golf apparel rental market.

In this study, we investigated the anti-hypertensive properties of mulberry products by modulating the renin–angiotensin system (RAS). Comparative analysis showed that the ethyl acetate fractions, particularly from the Cheongil and Daeshim cultivars, contained the highest levels of polyphenols and flavonoids, with concentrations reaching 110 mg gallic acid equivalent (GE)/g and 471 mg catechin equivalent (CE)/g of extract, respectively. The ethyl acetate fraction showed superior angiotensin-converting enzyme (ACE) inhibitory activity, mainly because of the presence of the prenylated flavonoids kuwanon G and H. UPLC/Q-TOF-MS analysis identified kuwanon G and H as the primary active components, which significantly contributed to the pharmacological efficacy of the extract. In vivo testing of mice fed a high-salt diet showed that the ethyl acetate fraction substantially reduced the heart weight and lowered the serum renin and angiotensinogen levels by 34% and 25%, respectively, highlighting its potential to modulate the RAS. These results suggested that the ethyl acetate fraction of mulberry root bark is a promising candidate for the development of natural ACE inhibitors. This finding has significant implications for the management of hypertension through RAS regulation and the promotion of cardiovascular health in the functional food industry.

Heterotopic ossification (HO) is a debilitating pathology where ectopic bone develops in areas of soft tissue. HO can develop as a consequence of traumatic insult or as a result of dysregulated osteogenic signaling, as in the case of the orphan disease fibrodysplasia ossificans progressiva (FOP). Traumatic HO (tHO) formation is mediated by the complex interplay of signaling between progenitor, inflammatory, and nerve cells, among others, making it a challenging process to understand. Research into the pathogenesis of genetically mediated HO (gHO) in FOP has established a pathway involving uninhibited activin-like kinase 2 receptor (ALK2) signaling that leads to downstream osteogenesis. Current methods of diagnosis and treatment lag behind pre-mature HO detection and progressive HO accumulation, resulting in irreversible decreases in range of motion and chronic pain for patients. As such, it is necessary to draw on advancements made in the study of tHO and gHO to better diagnose, comprehend, prevent, and treat both.

Metaplastic carcinoma of the breast is a heterogeneous group of neoplasms with mixed epithelial and mesenchymal differentiation. Metaplastic carcinoma of the breast is a rare and aggressive malignancy, with high recurrence and metastasis. Metaplastic carcinoma with chondroid differentiation is an uncommon subtype that tends to have a relatively good prognosis than that of other subtypes. We report the imaging features of three cases of pathologically proven metaplastic carcinoma with chondroid differentiation as follows: a high-density mass with amorphous or coarse heterogeneous calcifications on mammography; a microlobulated or partially indistinct, complex cystic, and solid mass on sonography; and a relatively circumscribed or partially indistinct, irregular mass with heterogeneous T2 high-signal intensity and heterogeneous or rim enhancement with initial fast enhancement and delayed washout on MRI.

Background/Aim Transforming growth factor-beta (TGF-β) has a dichotomous role, functioning as a tumor suppressor and tumor promoter. TGF-β signatures, explored in mouse hepatocytes, have been reported to predict the clinical outcomes of hepatocellular carcinoma (HCC) patients; HCCs exhibiting early TGF-β signatures showed a better prognosis than those with late TGF-β signatures. The expression status of early and late TGF-β signatures remains unclear in defined lesions of human B-viral multistep hepatocarcinogenesis. Methods The expression of TGF-β signatures, early and late responsive signatures of TGF-β were investigated and analyzed for their correlation in cirrhosis, low-grade dysplastic nodules (DNs), high-grade DNs, early HCCs and progressed HCCs (pHCCs) by real-time PCR and immunohistochemistry. Results The expression levels of TGF-β signaling genes (TGFB1, TGFBR1, TGFBR2 and SMAD4) gradually increased with the progression of hepatocarcinogenesis, peaking in pHCCs. The expression of early responsive genes of TGF-β (GADD45B, FBP1, CYP1A2 and CYP3A4) gradually decreased, and that of the late TGF-β signatures (TWIST and SNAI1) significantly increased according to the progression of multistep hepatocarcinogenesis. Furthermore, mRNA levels of TWIST and SNAI1 were well correlated with those of stemness markers, with upregulation of TGF-β signaling, whereas FBP1 expression was inversely correlated with that of stemness markers. Conclusions The enrichment of the late responsive signatures of TGF-β with induction of stemness is considered to be involved in the progression of the late stage of multistep hepatocarcinogenesis, whereas the early responsive signatures of TGF-β are suggested to have tumor-suppressive roles in precancerous lesions of the early stage of multistep hepatocarcinogenesis.

BackgroundFatigue is one of the most common subjective symptoms that impairs daily life and predict health-related events. This study aimed to estimate the prevalence of fatigue in the global population.MethodsPubMed and the Cochrane Library were used to search for relevant articles from inception to December 31, 2021. Studies with prevalence data of fatigue in the general population were selected and reviewed by three authors independently and cross-checked. Regarding subgroups, adults (≥18 years), minors (