Differential Diagnosis of Pancreatic Cancer and its Mimicking Lesions.

Pancreatic cancer is usually detected through contrast-enhanced CT and MRI. However, pancreatic cancer is occasionally overlooked because of its small size or is misdiagnosed as other conditions due to atypical imaging features that present diagnostic challenges. Considering the rapid growth and poor prognosis associated with pancreatic cancer, the ability to accurately detect and differentiate pancreatic lesions is crucial for appropriate surgical intervention. Reviewing diverse challenging cases of pancreatic cancer at an early stage and other mimicking lesions may help us accurately interpret the imaging features of pancreatic cancer on CT and MRI scans. Therefore, we aimed to illustrate various imaging features of pancreatic cancer and its mimicking lesions and provide valuable insights for differential diagnosis.

Poly(ß-amino ester) polymer library with monomer variation for mRNA delivery.

Non-viral vectors for mRNA delivery primarily include lipid nanoparticles (LNPs) and polymers. While LNPs are known for their high mRNA delivery efficiency, they can induce excessive immune responses and cause off-target effects, potentially leading to side effects. In this study, we aimed to explore polymer-based mRNA delivery systems as a viable alternative to LNPs, focusing on their mRNA delivery efficiency and potential application in mRNA vaccines. We created a library of poly(ß-amino ester) (PBAE) polymers by combining various amine monomers and acrylate monomers. Through screening this polymer library, we identified specific polymer nanoparticles (PNPs) that demonstrated high mRNA expression efficiency, with sustained mRNA expression for up to two weeks. Furthermore, the PNPs showed mRNA expression only at the injection site and did not exhibit liver toxicity. Additionally, when assessing immune activation, the PNPs significantly induced T-cell immune activation and were effective in the plaque reduction neutralization test. These results suggest that polymer-based mRNA delivery systems not only hold potential for use in mRNA vaccines but also show promise for therapeutic applications.

Genetic diversity and structure of Persicaria amphibia (Polygonaceae) in South Korea using genotyping by sequencing.

BACKGROUND: Persicaria amphibia, a member of the Polygonaceae family, exists both aquatic and terrestrial forms. It is native to North America, Asia, Europe, and some parts of Africa. OBJECTIVE: This study aimed to determine the genetic diversity within and among populations of P. amphibia and the distribution characteristics of each population to investigate insights into the genetic structure and conservation of P. amphibia. METHODS: In this study, the genetic diversity and structure of 84 P. amphibia individuals from 7 populations in South Korea were analyzed using genotyping-by-sequencing (GBS). We used 2,469 single nucleotide polymorphisms (SNPs) to analyze genetic diversity, principal components, structure, and phylogeny. RESULTS: Our results showed a mean observed heterozygosity and mean expected heterozygosity of 0.34409 and 0.34082, respectively. Genetic diversity analysis indicated that the variation among populations (60.08%) was greater than that within populations (39.92%). Fixation index values, principal components analysis, structure, and phylogeny analyses showed that the population in Gyodongdo, Ganghwa Island was highly different. CONCLUSION: These results provide important insights for better understand the population history and genetic structure of P. amphibia.

Ubiquitin regulatory X (UBX) domain-containing protein 6 is essential for autophagy induction and inflammation control in macrophages.

Ubiquitin regulatory X (UBX) domain-containing protein 6 (UBXN6) is an essential cofactor for the activity of the valosin-containing protein p97, an adenosine triphosphatase associated with diverse cellular activities. Nonetheless, its role in cells of the innate immune system remains largely unexplored. In this study, we report that UBXN6 is upregulated in humans with sepsis and may serve as a pivotal regulator of inflammatory responses via the activation of autophagy. Notably, the upregulation of UBXN6 in sepsis patients was negatively correlated with inflammatory gene profiles but positively correlated with the expression of Forkhead box O3, an autophagy-driving transcription factor. Compared with those of control mice, the macrophages of mice subjected to myeloid cell-specific UBXN6 depletion exhibited exacerbated inflammation, increased mitochondrial oxidative stress, and greater impairment of autophagy and endoplasmic reticulum-associated degradation pathways. UBXN6-deficient macrophages also exhibited immunometabolic remodeling, characterized by a shift to aerobic glycolysis and elevated levels of branched-chain amino acids. These metabolic shifts amplify mammalian target of rapamycin pathway signaling, in turn reducing the nuclear translocation of the transcription factor EB and impairing lysosomal biogenesis. Together, these data reveal that UBXN6 serves as an activator of autophagy and regulates inflammation to maintain immune system suppression during human sepsis.

Allergen Sensitization and Its Association With Allergic Diseases in the Korean Population: Results From the 2019 Korea National Health and Nutrition Examination Survey.

PURPOSE: Allergen exposure is the most potent factor in allergen sensitization, which affects the exacerbation and severity of allergic diseases. Due to industrialization and climate change, the pattern of allergen sensitization has changed over time, and the incidence of allergic diseases has also increased. This study investigated the status of allergen sensitization in the Korean population and its effects on allergic diseases. METHODS: A total of 2,386 participants aged ≥ 10 years, who underwent 7 specific immunoglobulin E tests for aeroallergens (Dermatophagoides farinae [Der f], dog dander, cat epithelium, birch, oak, Japanese hop, and ragweed), were selected among the participants of the 2019 Korean National Health and Nutrition Examination Survey. We compared the demographic characteristics, combined allergic diseases, and sinusitis symptoms between the atopic and non-atopic groups. RESULTS: The prevalence of allergen sensitization in the general Korean population was 45%, and Der f was the most frequent cause of sensitization (39.9%). The prevalence of sensitization to indoor allergens was highest among teenagers and those belonging to the 20- to 29-year age group (P < 0.001). In contrast, there was a high prevalence of sensitization to outdoor allergens among individuals belonging to the age group of 60-69 years. The prevalence of atopic dermatitis (odds ratio [OR], 2.559; 95% confidence interval [CI], 1.689-3.878), allergic rhinitis (OR, 3.075; 95% CI, 2.426-3.897), and otitis media (OR, 1.481; 95% CI, 1.092-2.007) significantly increased by allergen sensitization. Patients with allergen sensitization were more likely to experience the symptoms of rhinitis and sinusitis. CONCLUSIONS: The study findings confirmed that allergen sensitization occurs in approximately half of the general Korean population and affects the prevalence and symptoms of allergic diseases. This suggests that active allergy tests and diagnosis of allergic diseases are necessary in Koreans.

Midkine as a driver of age-related changes and increase in mammary tumorigenesis.

Aging is a pivotal risk factor for cancer, yet the underlying mechanisms remain poorly defined. Here, we explore age-related changes in the rat mammary gland by single-cell multiomics. Our findings include increased epithelial proliferation, loss of luminal identity, and decreased naive B and T cells with age. We discover a luminal progenitor population unique to old rats with profiles reflecting precancerous changes and identify midkine (Mdk) as a gene upregulated with age and a regulator of age-related luminal progenitors. Midkine treatment of young rats mimics age-related changes via activating PI3K-AKT-SREBF1 pathway and promotes nitroso-N-methylurea-induced mammary tumorigenesis. Midkine levels increase with age in human blood and mammary epithelium, and higher MDK in normal breast tissue is associated with higher breast cancer risk in younger women. Our findings reveal a link between aging and susceptibility to tumor initiation and identify midkine as a mediator of age-dependent increase in breast tumorigenesis.

Exploring the concept of disease control in chronic cough.

Background: Disease control in chronic diseases is an overarching concept that reflects the degree to which the goals of therapy are met. However, to date, there is no consensus on the definition of disease control in chronic cough. This study aimed to provide a conceptual exploration of patient-reported cough control in chronic cough. Methods: This research is comprised of two subanalyses. First, patients with chronic cough receiving care at referral clinics were evaluated. Correlation analyses were performed between patient-reported cough control (a 5-point Likert scale), cough-specific patient-reported outcomes (PROs) and generic health PRO scores. Second, a survey was conducted among patients with refractory chronic cough and physicians to identify factors pertinent to cough control. Results: The analysis of 341 patients (mean age: 55.5±15.1 years; female: 66.6%) revealed that cough control rating was moderately correlated with cough severity visual analogue scale and Leicester Cough Questionnaire scores, while demonstrating weaker correlations with cough-associated throat symptoms, cough-related complications or general health-related quality of life (QoL). In the survey of patients and physicians, both groups considered certain factors, such as cough frequency, severity and impact on QoL, to be relevant to the concept of cough control. However, patients rated "need for cough rescue drug" notably higher than physicians. Conclusion: Patient-reported cough control was associated with cough severity or impact on QoL; however, cough control may not be fully captured by conventional cough PRO measurement tools. Further studies are warranted to define the consensus and tools to measure disease control in chronic cough.

Application of metabolic phase-specific modified nutrition risk in critically ill score: a prospective observational study in critically ill patients.

Background and aims: The prevalence of malnutrition in intensive care units (ICU) is high and can be caused by poor intake or absorption of nutrients in the digestive track, as well as disease-related inflammation. As strong catabolism restricts nutrient supply and potentially leads to subsequent malnutrition, appropriate nutrition should be provided based on the metabolic status. However, nutritional support strategies for considering the metabolic phase are not well established. Therefore, this study aimed to establish a strategy for nutritional support in each phase by implementing a phase-specific modified Nutrition Risk in Critically Ill (mNUTRIC) score. Methods: This prospective observational study was conducted on all adult patients admitted to the medical ICU for at least 36 h at Seoul National University Bundang Hospital between September 2020 and September 2022. Patient nutrition assessment (mNUTRIC score), clinical information, and nutritional supply (calories and proteins) were measured twice, in the acute phase (measured at 2 days) and late phase (measured at 7 days). The relationship between nutritional supply and 28-day mortality was analyzed using multiple logistic regression according to the mNUTRIC score in the acute and late phases. Risk factors related to 28-day mortality were analyzed using univariate and multivariate Cox proportional hazards regressions. Results: Of the 631 patients admitted to the ICU during the study period, 613 were included in the acute phase and 361 patients were included in the late phase. Nutritional supply was associated with 28-day mortality, with high mNUTRIC scores in both the acute and late phases. Cox proportional hazards regression analysis demonstrated that a high mNUTRIC score [hazard ratio (HR) 3.20 and 2.52, respectively], lactate >2.5 mg/dL were independent risk factors in both the acute and late phases. In addition, Albumin <2.5 mg/dL, the presence of neoplasm, and the need for dialysis in the acute phase, calorie adequacy <0.7 in the late phase (HR, 2.19) were identified as additional risk factors. Conclusion: The mNUTRIC score is a suitable tool for identifying critically ill patients who benefit from nutritional support. Nutritional supply should be considered for patients with high mNUTRIC scores in both the acute and late phases; however, careful supply should be provided in the acute phase and sufficient supply should be provided in the late phase.

Tinnitus Generation and Behavioral Changes Caused by Chronic Stress: A Behavioral and Brain Study in a Rat Model.

OBJECTIVES: This study explores the connection between chronic stress and tinnitus, a phantom auditory perception, using an animal model. METHODS: Rats were subjected to 2 h of daily restraint stress for 10 days. Tinnitus was assessed on the last day of stress exposure using the gap response of pre-pulse inhibition acoustic reflex, measured at 60 dB background sound level at 8, 16, and 20 kHz. Chronic stress-exposed rats were categorized into two groups: tinnitus (RTG) and non-tinnitus (RNTG). Various tests, including hearing assessments (distortion product otoacoustic emissions and auditory brainstem response), behavioral evaluations (elevated plus maze test and forced swimming test), and immunohistochemical studies in the auditory and limbic brain regions, were conducted to understand the relationship between chronic stress, tinnitus, and behavioral changes. RESULTS: Following chronic restraint stress, 64.3% of the rats exhibited tinnitus with no audiometric changes. EPM and FST indicated an increase of anxiety- and depression-related behavior in RTG. Immunohistochemical analyses identified specific alterations in the expression of neurotransmitter receptors within brain regions implicated in tinnitus. Specifically, we observed a decrease in γ-aminobutyric acid A receptor α1 expression and an increase in glutamate receptor (N-methyl-D-aspartate receptor subunit 1 and receptor subunit 2B) expression in specific brain region. These changes suggest a reorganization of neural circuits associated with the tinnitus generation and behavioral changes of the rats after chronic stress exposure. CONCLUSION: Chronic stress alone can be a causal factor for the generation of tinnitus and behavioral changes through altered neural activities in tinnitus-related brain networks. LEVEL OF EVIDENCE: NA Laryngoscope, 2024.

Elevated Circulating Sclerostin Levels in Frail Older Adults: Implications beyond Bone Health.

Background: Sclerostin, initially recognized for its pivotal role in bone metabolism, has gained attention for its multifaceted impact on overall human health. However, its influence on frailty-a condition that best reflects biological age-has not been thoroughly investigated. Methods: We collected blood samples from 244 older adults who underwent comprehensive geriatric assessments. Sclerostin levels were quantified using an enzyme-linked immunosorbent assay. Frailty was assessed using two validated approaches: the phenotypic model by Fried and the deficit accumulation frailty index (FI) by Rockwood. Results: After controlling for sex, age, and body mass index, we found that serum sclerostin levels were significantly elevated in frail individuals compared to their robust counterparts (P<0.001). There was a positive correlation between serum sclerostin concentrations and the FI (P<0.001). Each standard deviation increase in serum sclerostin was associated with an odds ratio of 1.87 for frailty (P=0.003). Moreover, participants in the highest quartile of sclerostin levels had a significantly higher FI and a 9.91-fold increased odds of frailty compared to those in the lowest quartile (P=0.003 and P=0.039, respectively). Conclusion: These findings, which for the first time explore the association between circulating sclerostin levels and frailty, have significant clinical implications, positioning sclerostin as one of potential blood-based biomarkers for frailty that captures the comprehensive physical, mental, and social aspects of the elderly, extending beyond its traditional role in bone metabolism.

Agrobacterium-mediated Cuscuta campestris transformation as a tool for understanding plant-plant interactions.

Cuscuta campestris, a stem parasitic plant, has served as a valuable model plant for the exploration of plant-plant interactions and molecular trafficking. However, a major barrier to C. campestris research is that a method to generate stable transgenic plants has not yet been developed. Here, we describe the development of a Cuscuta transformation protocol using various reporter genes (GFP, GUS, or RUBY) and morphogenic genes (CcWUS2 and CcGRF/GIF), leading to a robust protocol for Agrobacterium-mediated C. campestris transformation. The stably transformed and regenerated RUBY C. campestris plants produced haustoria, the signature organ of parasitic plants, and these were functional in forming host attachments. The locations of T-DNA integration in the parasite genome were confirmed through TAIL-PCR. Transformed C. campestris also produced flowers and viable transgenic seeds exhibiting betalain pigment, providing proof of germline transmission of the RUBY transgene. Furthermore, RUBY is not only a useful selectable marker for the Agrobacterium-mediated transformation, but may also provide insight into the movement of molecules from C. campestris to the host during parasitism. Thus, the protocol for transformation of C. campestris reported here overcomes a major obstacle to Cuscuta research and opens new possibilities for studying parasitic plants and their interactions with hosts.

Correction: Park et al. Licoricidin, an Active Compound in the Hexane/Ethanol Extract of Glycyrrhiza uralensis, Inhibits Lung Metastasis of 4T1 Murine Mammary Carcinoma Cells. Int. J. Mol. Sci. 2016, 17, 934.

In the original publication [...].

Enhanced Soil Fertility and Carbon Dynamics in Organic Farming Systems: The Role of Arbuscular Mycorrhizal Fungal Abundance.

Arbuscular mycorrhizal fungi (AMF) are critical for soil ecosystem services as they enhance plant growth and soil quality via nutrient cycling and carbon storage. Considering the growing emphasis on sustainable agricultural practices, this study investigated the effects of conventional and organic farming practices on AMF diversity, abundance, and ecological functions in maize, pepper, and potato-cultivated soils. Using next-generation sequencing and quantitative PCR, we assessed AMF diversity and abundance in addition to soil health indicators such as phosphorus content, total nitrogen, and soil organic carbon. Our findings revealed that, while no significant differences in soil physicochemical parameters or AMF diversity were observed across farming systems when all crop data were combined, organic farming significantly enhances AMF abundance and fosters beneficial microbial ecosystems. These ecosystems play vital roles in nutrient cycling and carbon storage, underscoring the importance of organic practices in promoting robust AMF communities that support ecosystem services. This study not only deepens our understanding of AMF's ecological roles but also highlights the potential of organic farming to leverage these benefits for improving sustainability in agricultural practices.

Novel Therapeutic Effects of Euphorbia heterophylla L. Methanol Extracts in Macular Degeneration Caused by Blue Light in A2E-Laden ARPE-19 Cells and Retina of BALB/c Mice.

Natural products with high antioxidant activity are considered as innovative prevention strategies to effectively prevent age-related macular degeneration (AMD) in the early stage because the generation of reactive oxygen species (ROS) leading to the development of drusen is reported as an important cause of this disease. To investigate the prevention effects of the methanol extracts of Euphorbia heterophylla L. (MEE) on AMD, its effects on the antioxidant activity, inflammatory response, apoptosis pathway, neovascularization, and retinal tissue degeneration were analyzed in N-retinylidene-N-retinylethanolamine (A2E)-landed spontaneously arising retinal pigment epithelia (ARPE)-19 cells and BALB/c mice after exposure to blue light (BL). The MEE contained 10 active components and showed high free radical scavenging activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and nitric oxide (NO) radicals. The pretreatments of high-dose MEE remarkably suppressed the production of intracellular ROS (88.2%) and NO (25.2%) and enhanced (SOD) activity (84%) and the phosphorylation of nuclear factor erythroid 2-related factor 2 (Nrf2) in A2E + BL-treated ARPE-19 cells compared to Vehicle-treated group. The activation of the inducible nitric oxide synthase (iNOS)-induced cyclooxygenase-2 (COX-2) mediated pathway, inflammasome activation, and expression of inflammatory cytokines was significantly inhibited in A2E + BL-treated ARPE-19 cells after the MEE pretreatment. The activation of the apoptosis pathway and increased expression of neovascular proteins (36% for matrix metalloproteinase (MMP)-9) were inhibited in the MEE pretreated groups compared to the Vehicle-treated group. Furthermore, the thickness of the whole retina (31%), outer nuclear layer (ONL), inner nuclear layer (INL), and photoreceptor layer (PL) were significantly increased by the MEE pretreatment of BALB/c mice with BL-induced retinal degeneration. Therefore, these results suggest that the MEE, with its high antioxidative activity, protects against BL-induced retinal degeneration through the regulation of the antioxidative system, inflammatory response, apoptosis, and neovascularization in the AMD mouse model.

Production of Terpene Trilactones from Cell and Organ Cultures of Ginkgo biloba.

Ginkgo biloba is an ancient plant that has survived up until the present day. Gingko biloba is a rich source of valuable secondary metabolites, particularly terpene trilactones (TTLs) such as ginkgolides and bilobalides, which are obtained from the leaves and seeds of the plant. TTLs have pharmacological properties, including anticancer, anti-dementia, antidepressant, antidiabetic, anti-inflammatory, anti-hypertensive, antiplatelet, immunomodulatory, and neuroprotective effects. However, ginkgo is a very-slow-growing tree that takes approximately 30 years to reach maturity. In addition, the accumulation of TTLs in these plants is affected by age, sex, and seasonal and geographical variations. Therefore, plant cell cultures have been established in ginkgo to produce TTLs. Extensive investigations have been conducted to optimize the culture media, growth regulators, nutrients, immobilization, elicitation, and precursor-feeding strategies for the production of TTLs in vitro. In addition, metabolic engineering and synthetic biology methods have been used for the heterologous production of TTLs. In this review, we present the research strategies applied to cell cultures for the production of TTLs.

14K prolactin derived 14-mer antiangiogenic peptide targets bradykinin-/nitric oxide-cGMP-dependent angiogenesis.

Over the past few decades, VEGF-targeted antiangiogenic therapy for cancers has gained increasing attention. Nevertheless, there are still several limitations such as the potential resistance mechanisms arising in cancer cells against these therapies and their potential adverse effects. These limitations highlight the need for novel anti-angiogenesis molecules and better understanding of the mechanisms of tumor angiogenesis. In the present study, we investigated the antiangiogenic properties of a novel 14-mer antiangiogenic peptide (14-MAP) derived from N-terminal 14 kDa buffalo prolactin and characterized its mode of action. 14-MAP at the picomolar concentration inhibited VEGF- and bradykinin (an autacoid peptide expressed in vascular tissues in pathophysiology, BK)-stimulated endothelial nitric oxide (eNO) production, cell migration, and proliferation in endothelial cells and vessel development in the chick embryo. Although this peptide inhibited both VEGF- and BK-dependent angiogenic processes, its action was more pronounced in the latter. Moreover, the interference of 14-MAP with the eNO synthase (eNOS)-cyclic GMP pathway was also identified. A combination of a low dose of Avastin, a widely used drug targeting VEGF-dependent angiogenesis, and 14-MAP significantly reduced tumor size in an in vivo model of human colon cancer. Taken together, our results suggest that 14-MAP, a BK- and eNOS-dependent antiangiogenic peptide, might be useful for overcoming the limitation of VEGF-targeted antiangiogenic therapy in cancer patients. However, further studies will be required to further characterize its mode of action and therapeutic potential.

Effect of biologic therapies on quality of life in severe asthma: Findings from the PRISM study.

Background: Anti-type 2 (T2) biologic therapies (biologics) improve exacerbation rates, lung function, and asthma-related quality of life (QoL) in patients with severe T2 asthma. However, studies comparing different biologics are lacking. We evaluated the QoL in patients with severe asthma comprehensively and compare the efficacy of different T2-directed biologics using QoL questionnaires. Methods: We compared the QoL between severe and mild-to-moderate asthma and between severe asthma with and without biologics treatment. Data of mild-to-moderate were extracted from the Cohort for Reality and Evolution of Adult Asthma in Korea, and data of severe asthma were collected from the Precision Medicine Intervention in Severe Asthma. We included 183 patients with severe asthma treated with T2 biologics or conventional therapy between April 2020 and May 2021 and assessed QoL of them using the Questionnaire for Adult Korean Asthmatics (QLQAKA), Severe Asthma Questionnaire (SAQ), and EuroQoL-5Dimensions (EQ-5D) at baseline and 6 months. Results: The EQ-5D index (0.803) of severe asthma was lower than that of other chronic diseases representing a worse QoL. The scores for all questions of QLQAKA, except "cough," were lower (less control) in the severe asthma group than in the mild-to-moderate asthma group at baseline and 6 months (P < 0.05). The total scores and subscores of all domains of the QLQAKA, SAQ, and EQ-5D improved significantly 6 months after biologic therapy but not after conventional therapy. The total QLQAKA, SAQ, and EQ-5D scores improved after 6 months in the anti-IL-5 (P < 0.05) and anti-IL-4/IL-13 (P < 0.05) treatment groups with no significant difference between groups (P > 0.05). Conclusion: QoL was worse in severe asthma than in mild-to-moderate asthma and other chronic diseases. T2 biologics equally improved QoL in patients with severe asthma.