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Background: The density of tumor-associated macrophages in the tumor microenvironment of anaplastic thyroid cancer (ATC) is associated with poor prognosis. However, the crosstalk between macrophages and ATC cells is poorly understood. This study aimed to examine the impact of macrophages on cancer cell phenotypes. We found a new mediator between M2 macrophages and ATC cells through proteomics analysis. Methods: The role of macrophages in proliferation, migration, and invasion of ATC cells was evaluated using coculture assay and conditioned medium (CM). Secretory factors in the CM from single or coculture were identified using liquid chromatography-tandem mass spectrometry proteomics analysis. We evaluated the role of the secretory factor in proliferation, migration, and invasion of cancer cells. In vivo xenograft model was used to evaluate the effect of the factor. Results: M2 macrophages significantly increased the proliferation, migration, and invasion of ATC cells, whereas M1 macrophages decreased the proliferation, migration, and invasion of ATC cells. Based on proteomic analysis of CM, we identify carboxypeptidase A4 (CPA4) as a mediator of the crosstalk between macrophages and ATC cells. CPA4 was only detected in the coculture media of M2 macrophage/8505C, and its expression in cancer cells increased by M2 macrophage. The expression of CPA4 protein was significantly higher in human thyroid cancers, particularly in ATCs, than normal and benign tissues. A bioinformatics analysis of public data revealed that CPA4 expression was associated with poor prognosis and dedifferentiation of thyroid cancer. Knockdown of CPA4 suppressed proliferation, colony formation, migration, and invasion of ATC cells, consistent with the decrease of STAT3, ERK, and AKT/mTOR phosphorylation and epithelial-mesenchymal transition (EMT) marker expression. In addition, the increased expression of CPA4 in cancer cells by M2 macrophage stimulation induced the polarization of macrophages to the M2 phenotype, which formed a positive feedback loop. Xenograft tumors did not develop after CPA4 knockdown. Conclusions: Our data suggest that CPA4 stimulates the progression of thyroid cancer by mediating between M2 macrophages and ATC cells. CPA4 can be a new therapeutic target for the treatment of patients with ATC. [ABSTRACT FROM AUTHOR]

Secreted signaling peptides are central regulators of growth, development, and stress responses, but specific steps in the evolution of these peptides and their receptors are not well understood. Also, the molecular mechanisms of peptide-receptor binding are only known for a few examples, primarily owing to the limited availability of protein structural determination capabilities to few laboratories worldwide. Plants have evolved a multitude of secreted signaling peptides and corresponding transmembrane receptors. Stress-responsive SERINE RICH ENDOGENOUS PEPTIDES (SCOOPs) were recently identified. Bioactive SCOOPs are proteolytically processed by subtilases and are perceived by the leucine-rich repeat receptor kinase MALE DISCOVERER 1-INTERACTING RECEPTOR-LIKE KINASE 2 (MIK2) in the model plant Arabidopsis thaliana. How SCOOPs and MIK2 have (co)evolved, and how SCOOPs bind to MIK2 are unknown. Using in silico analysis of 350 plant genomes and subsequent functional testing, we revealed the conservation of MIK2 as SCOOP receptor within the plant order Brassicales. We then leveraged AI-based structural modeling and comparative genomics to identify two conserved putative SCOOP-MIK2 binding pockets across Brassicales MIK2 homologues predicted to interact with the "SxS" motif of otherwise sequence-divergent SCOOPs. Mutagenesis of both predicted binding pockets compromised SCOOP binding to MIK2, SCOOP-induced complex formation between MIK2 and its coreceptor BRASSINOSTEROID INSENSITIVE 1-ASSOCIATED KINASE 1, and SCOOP-induced reactive oxygen species production, thus, confirming our in silico predictions. Collectively, in addition to revealing the elusive SCOOP-MIK2 binding mechanism, our analytic pipeline combining phylogenomics, AI-based structural predictions, and experimental biochemical and physiological validation provides a blueprint for the elucidation of peptide ligand-receptor perception mechanisms. [ABSTRACT FROM AUTHOR]

A female narrow-ridged finless porpoise (Neophocaena asiaeorientalis) stranded on a beach on Jeju Island showed epithelial proliferative skin lesions on its body. Two false killer whales (Pseudorca crassidens), caught using nets near Gangneung and Samcheok, respectively, had multiple plaques on their penile epidermis. Histological examination of the epidermis revealed that all the lesions had common features, including accentuated rete pegs, ballooning changes, and eosinophilic intranuclear inclusion (INI) bodies. Based on the histopathological results, herpesvirus infection was suspected, and thus further analysis was conducted using herpesvirus-specific primers. Based on nested polymerase chain reaction (PCR) tests using the herpesvirus-detectable primers, the PCR products demonstrated two fragments: a 222-base-pair (bp) sequence of the DNA polymerase gene, SNUABM_CeHV01, showing 96.4% identity with a bottlenose dolphin herpesvirus from the Jeju narrow-ridged finless porpoise; and a 222 bp sequence of the DNA polymerase gene, SNUABM_CeHV02, showing 95.95% identity with the same bottlenose dolphin herpesvirus from the Gangneung and Samcheok false killer whales. The significance of this study lies in its ability to demonstrate the existence of novel cetacean herpesviruses in South Korean seawater, representing an important step forward in studying potentially harmful pathogens that affect endangered whale and dolphin populations. [ABSTRACT FROM AUTHOR]

Background: The impact of long-term chronic periodontal conditions on the risk of lung cancer could not be accurately evaluated. Our aim was to provide more evidence on the connection between chronic periodontitis (CP) and lung cancer using a nationwide dataset. Methods: This study used data from the Korean National Health Insurance Service National Sample Cohort. We enrolled 72,658 individuals with CP (CP cohort) between 2005 and 2019 and 1:1 age- and sex-matched controls without CP (non-CP cohort). Results: During the median follow-up period of 5.1 (interquartile range, 2.8-8.0) years, 0.56% (n = 405/72,658) of the CP cohort and 0.29% (n = 212/72,658) of the matched non-CP cohort developed lung cancer, with incidence rates of 8.3 and 4.5 per 10,000 person-years. The risk of incident lung cancer was significantly higher in the CP cohort than in the matched non-CP cohort (adjusted hazard ratio = 2.27, 95% confidence interval = 1.94-2.65). The risk of incident lung cancer was 2.45-fold and 2.10-fold higher in mild and moderate-to-severe CP cohorts than in the matched non-CP control. The risk of incident lung cancer was especially higher in the 40-59 age group, females, and never-smokers than their counterparts. Conclusion: We demonstrate that the risk of incident lung cancer is higher in individuals with CP than in those without. The risk of lung cancer was especially high in individuals with more severe CP, females, never-smokers, and obese populations. [ABSTRACT FROM AUTHOR]

Background: This study examines integrating physical and mental healthcare for disadvantaged persons with type 2 diabetes mellitus and mild-to-moderate depression in the community, using a mobile application within a public-private-academic partnership. Methods: The Korean Diabetes Association has developed a mobile application combining behavioral activation for psychological well-being and diabetes self-management, with conventional medical therapy. Participants were randomly assigned to receive the application with usual care or only usual care. Primary outcomes measured changes in psychological status and diabetes selfmanagement through questionnaires at week 12 from the baseline. Secondary outcomes assessed glycemic and lipid control, with psychological assessments at week 16. Results: Thirty-nine of 73 participants completed the study (20 and 19 in the intervention and control groups, respectively) and were included in the analysis. At week 12, the intervention group showed significant reductions in depression severity and perceived stress compared to the control group. Additionally, they reported increased perceived social support and demonstrated improved diabetes self-care behavior. These positive effects persisted through week 16, with the added benefit of reduced anxiety. While fasting glucose levels in the intervention group tended to improve, no other significant differences were observed in laboratory assessments between the groups. Conclusion: This study provides compelling evidence for the potential efficacy of a mobile application that integrates physical and mental health components to address depressive symptoms and enhance diabetes self-management in disadvantaged individuals with type 2 diabetes mellitus and depression. Further research involving larger and more diverse populations is warranted to validate these findings and solidify their implications. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to compare the prevalence of dysphonia and dysphagia among adults in the United States between 2012 and 2022. Method: A retrospective and cross-sectional design with national surveys was used. The 2012 and 2022 National Health Interview Surveys were utilized to estimate the number of adults reporting dysphonia and dysphagia in the past 12 months. Multivariate logistic regression models were used to examine associations between the survey year (2022 vs. 2012) and the prevalence rate of dysphonia and dysphagia while accounting for demographics and clinical characteristics. Results: The population-estimated mean age was 46.63 years in 2012, which increased to 48.12 years in 2022. In 2012, adults reporting dysphonia and dysphagia were 17.89 million (7.62%) and 9.44 million (4.02%), respectively. In 2022, these estimates increased to 29.92 million adults (11.71%) and 15.10 million adults (5.91%), respectively. Adults in 2022 had significantly higher odds for reporting dysphonia (odds ratio [OR] = 1.602, 95% confidence intervals [CIs] [1.486, 1.726], p < .0001) and dysphagia (OR = 1.461, 95% CI [1.328, 1.606], p < .0001) in the past 12 months compared to adults in 2012. Conclusions: The population-estimates indicated that in 2022, dysphonia affected one in 8.5 adults and dysphagia affected one in 17 adults. The increase in prevalence of these disorders should serve as a call-to-action to improve access to care and research for voice and swallowing disorders. [ABSTRACT FROM AUTHOR]

The safety and efficacy of both cell and gene therapies have been demonstrated in numerous preclinical and clinical trials. Chimeric antigen receptor T (CAR-T) cell therapy, which leverages the technologies of both cell and gene therapies, has also shown great promise for treating various cancers. Advancements in pertinent fields have also highlighted challenges faced while manufacturing cell and gene therapy products. Potential problems and obstacles must be addressed to ease the clinical translation of individual therapies. Literature reviews of representative cell-based, gene-based, and cell-based gene therapies with regard to their general manufacturing processes, the challenges faced during manufacturing, and QC specifications are limited. We review the general manufacturing processes of cell and gene therapies, including those involving mesenchymal stem cells, viral vectors, and CAR-T cells. The complexities associated with the manufacturing processes and subsequent QC/validation processes may present challenges that could impede the clinical progression of the products. This article addresses these potential challenges. Further, we discuss the use of the manufacturing model and its impact on cell and gene therapy. [ABSTRACT FROM AUTHOR]

Background: Thyroid cancer is a slow-growing tumor with excellent oncological outcomes. However, few patients with unexpectedly severe outcomes are usually ignored. Current Concepts: Radioactive iodine therapy is the mainstay treatment for differentiated thyroid cancer with distant metastasis. The refractoriness to radioactive iodine therapy has been overcome by the emergence of targeted agents. First, multikinase inhibitors (sorafenib and lenvatinib) targeting the growth factor pathway were developed and approved as anticancer agents for patients with advanced differentiated thyroid cancer, regardless of their genetic features. With progress in sequencing techniques, the genetic backgrounds of tumors have unveiled new targets, including rearrangements during transformation and tropomyosin receptor kinase. Special attention should be paid to the national health insurance coverage of systemic therapeutics and genetic studies. Discussion and Conclusion: New drugs were introduced to treat previously untreatable advanced thyroid cancers. However, the cost of these drugs has increased with new developments, and only first-line drugs for thyroid cancer are still covered by insurance. These medical advances will remain an illusion for clinics and patients if improvements in healthcare policies do not accompany them. [ABSTRACT FROM AUTHOR]

Background: This study investigated the prevalence and subtype distribution of circulating tumor cells (CTCs) in patients with papillary thyroid cancer (PTC) before and after thyroidectomy to determine the potential of CTC count as a noninvasive marker of the efficacy of surgical treatment in PTC. Materials and methods: Between January 2021 and January 2022, 62 PTC patients who underwent thyroidectomy at Seoul National University Bundang Hospital were prospectively evaluated. Peripheral blood samples (7.5 ml) were collected from each patient for CTC analysis before surgery and at 2 weeks and 3 months after surgery. CTC count and the distribution of CTC subtypes, including epithelial, epithelial-mesenchymal, and mesenchymal phenotypes, were analyzed using the negative selection method and immunofluorescence staining. The relationship between CTC count and clinicopathological characteristics was analyzed before and after surgery. Results: Before surgery, CTCs were detected in 87% (54/62) of patients; the mean CTC count was 8.0 and the median was 5.0 in 7.5 ml of peripheral blood. The mesenchymal or epithelial-mesenchymal phenotypes were predominant. After thyroidectomy, the mean and median CTC count values decreased to 5.3 and 2.5, respectively, at 2 weeks and to 4.3 and 3.0, respectively, at 3 months. This postoperative reduction in CTCs was more pronounced in patients with lymphatic invasion, lymph node metastasis, or BRAF V600E mutation. Conclusion: CTCs were detected in patients with PTC with a predominance of cells undergoing epithelial-mesenchymal transition. The CTC count decreased postoperatively, suggesting that liquid biopsy with CTC detection could be a valuable noninvasive tool for monitoring the efficacy of surgery in PTC. [ABSTRACT FROM AUTHOR]

The actin-based cytoskeleton is considered a fundamental driving force for cell differentiation and development. Destrin (Dstn), a member of the actin-depolymerizing factor family, regulates actin dynamics by treadmilling actin filaments and increasing globular actin pools. However, the specific developmental roles of dstn have yet to be fully elucidated. Here, we investigated the physiological functions of dstn during early embryonic development using Xenopus laevis as an experimental model organism. dstn is expressed in anterior neural tissue and neural plate during Xenopus embryogenesis. Depleting dstn promoted morphants with short body axes and small heads. Moreover, dstn inhibition extended the neural plate region, impairing cell migration and distribution during neurulation. In addition to the neural plate, dstn knockdown perturbed neural crest cell migration. Our data suggest new insights for understanding the roles of actin dynamics in embryonic neural development, simultaneously presenting a new challenge for studying the complex networks governing cell migration involving actin dynamics. [ABSTRACT FROM AUTHOR]

Pleural metastasis is the most common cause of malignant diseases involving the pleura, and characterized by pleural effusion, nodules, and thickening. Pleuroparenchymal fibroelastosis (PPFE) is a disease characterized by apical pleural thickening and subjacent parenchymal fibrosis. We report a case of a 60-year-old male with lung cancer in the left lower lobe and underlying PPFE combined with left apical pleural metastasis. Initially, asymmetric left apical pleural thickening due to pleural metastasis was mistaken for PPFE. Additionally, we describe the imaging and histopathological findings of PPFE, including MRI findings. [ABSTRACT FROM AUTHOR]

A pulmonary artery periadventitial hematoma is a rare complication of a Stanford type A intramural hematoma. As the proximal ascending aorta and pulmonary artery share a common adventitial layer, extravasated blood from the intramural hematoma in the ascending thoracic aorta may extend to beneath the adventitia of the pulmonary artery. The authors describe a case involving a 66-year-old male with acute chest pain who presented with a pulmonary artery periadventitial hematoma associated with a Stanford type A intramural hematoma. [ABSTRACT FROM AUTHOR]