Imaging of the vascular distribution of the outer ear using optical coherence tomography angiography for highly accurate positioning of a hearable sensor.

Novel hearable technology is securely and comfortably positioned within the ear canal minimizing inaccuracies caused by accessory movements during activities. Despite extensive research on hearable technologies within the outer ear, there is a lack of research in the field of vascular imaging and quantitative analysis in the outer ear in vivo, which is one of the crucial factors to select the appropriate sensor position. Therefore, in this paper, we introduced optical coherence tomography angiography (OCTA)-based qualitative and quantitative analyses to visualize the inner vasculature of the outer ear to acquire vascular maps for microvascular assessments in vivo. By generating maximum amplitude projection images from three-dimensional blood vascular volume, we identified variations of blood vessel signal caused by the different biological characteristics and curvature of the ear among individuals. The performance of micro-vascular mapping using the proposed method was validated through the comparison and analysis of individual vascular parameters using extracted 20 vascular-related variables. In addition, we extracted pulsatile blood flow signals, demonstrating its potential to provide photoplethysmographic signals and ear blood maps simultaneously. Therefore, our proposed OCTA-based method for ear vascular mapping successfully provides quantitative information about ear vasculature, which is potentially used for determining the position of system-on-chip sensors for health monitoring in hearable devices.

Mebendazole preferentially inhibits cilia formation and exerts anticancer activity by synergistically augmenting DNA damage.

The cilium is a microtubule-based organelle that plays a pivotal role in embryonic development and maintenance of physiological functions in the human body. In addition to their function as sensors that transduce diverse extracellular signals, including growth factors, fluid flow, and physical forces, cilia are intricately involved in cell cycle regulation and preservation of DNA integrity, as their formation and resorption dynamics are tightly linked to cell cycle progression. Recently, several studies have linked defects in specific ciliary proteins to the DNA damage response. However, it remains unclear whether and how primary cilia contribute to cancer development. Mebendazole (MBZ) is an anthelmintic drug with anticancer properties in some cancer cells. MBZ is continuously being tested for clinical studies, but the precise mechanism of its anticancer activities remains unknown. Here, using Xenopus laevis embryos as a model system, we discovered that MBZ significantly hinders cilia formation and induces DNA damage. Remarkably, primary cilium-bearing cancer cells exhibited heightened vulnerability to combined treatment with MBZ and conventional anticancer drugs. Our findings shed light on the specific influence of MBZ on cilia, rather than cytosolic microtubules, in triggering DNA damage, elucidating a previously unidentified mechanism underlying potential MBZ-mediated cancer therapy.

Effect of collagen endometrial patch loaded with adipose-derived mesenchymal stem cells on endometrial regeneration in rats with a thin endometrium.

Background: This study aimed to investigate the effects of a collagen endometrial patch (EM patch) loaded with adipose-derived mesenchymal stem cells (ADSCs) on endometrial regeneration in a rat model with thin endometrium. Materials and methods: Thin endometrium was induced in female rats and divided into treatment groups as outlined: control, group 1(G1), local injection of ADSCs into the uterus, group 2 (G2), an EM patch without ADSCs, group 3 (G3), and an EM patch loaded with ADSCs, group 4 (G4). The rats were euthanized at either two weeks or four weeks after modeling and treatment followed by histological and biochemical analyses to examine the regenerative effects on the injured endometrium. Results: Transplantation of the ADSC-loaded EM patch significantly promoted endometrial proliferation and increased the luminal epithelial area. Two weeks after treatment, the mean number of von Villebrand factor (vWF)+ or cluster of differentiation (CD) 31+-stained blood vessels was significantly higher in G4 than in G1 and G2. The mRNA and protein expression levels of TGF-ß and FGF2 were significantly upregulated in G4 compared to those in the control. G4 exhibited significantly increased LIF mRNA levels and immunoreactivity compared with the other groups at both two weeks and four weeks after treatment. Cell tracking after ADSCs treatment revealed the presence of a substantial number of ADSCs grafted in the uterine tissues of G4, whereas a low number of ADSCs that were focally clustered were present in G2. Conclusion: Transplantation of EM patches loaded with ADSCs resulted in the histological and biochemical restoration of an injured endometrium. The strategic integration of EM patches and ADSCs holds significant promise as an innovative therapeutic approach for effectively treating impaired endometrial conditions.

Validation and Clinical Application of ONCOaccuPanel for Targeted Next-Generation Sequencing of Solid Tumors.

PURPOSE: Targeted next-generation sequencing (NGS) is widely used for simultaneously detecting clinically informative genetic alterations in a single assay. Its application in clinical settings requires the validation of NGS gene panels. In this study, we aimed to validate a targeted hybridization capture-based DNA panel (ONCOaccuPanel) using the Illumina MiSeq sequencing platform. The panel allows the simultaneous detection of single-nucleotide variants (SNVs), insertions, deletions, and copy number changes of 323 genes and fusions of 17 genes in solid tumors. Materials and Methods: We used 16 formalin-fixed paraffin-embedded (FFPE) tumor samples with previously known genetic mutations and one reference material (HD827) for validation. Moreover, we sequenced an additional 117 FFPE tumor samples to demonstrate the clinical utility of this panel. RESULTS: Validation revealed a 100% positive percentage agreement and positive predictive value for the detection of SNVs, insertions, deletions, copy number changes, fusion genes, and microsatellite instability-high types. We observed high levels of reproducibility and repeatability (R2 correlation coefficients=0.96-0.98). In the limit of detection assessment, we identified all clinically relevant genes with allele frequencies > 3%. Furthermore, the clinical application of ONCOaccuPanel using 117 FFPE samples demonstrated robust detection of oncogenic alterations. Oncogenic alterations and targetable genetic alterations were detected in 98.2% and 27.4% cases, respectively. CONCLUSION: ONCOaccuPanel demonstrated high analytical sensitivity, reproducibility, and repeatability and is feasible for the detection of clinically relevant mutations in clinical settings.

Genomic Effect of DNA Methylation on Gene Expression in Colorectal Cancer.

The aberrant expression of cancer-related genes can lead to colorectal cancer (CRC) carcinogenesis, and DNA methylation is one of the causes of abnormal expression. Although many studies have been conducted to reveal how DNA methylation affects transcription regulation, the ways in which it modulates gene expression and the regions that significantly affect DNA methylation-mediated gene regulation remain unclear. In this study, we investigated how DNA methylation in specific genomic areas can influence gene expression. Several regression models were constructed for gene expression prediction based on DNA methylation. Among these models, ElasticNet, which had the best performance, was chosen for further analysis. DNA methylation near transcription start sites (TSS), especially from 2 kb upstream to 7 kb downstream of TSS, had an essential regulatory role in gene expression. Moreover, methylation-affected and survival-associated genes were compiled and found to be mainly enriched in immune-related pathways. This study investigated genomic regions in which methylation changes can affect gene expression. In addition, this study proposed that aberrantly expressed genes due to DNA methylation can lead to CRC pathogenesis by the immune system.

Bactericidal Effect of Cecropin A Fused Endolysin on Drug-Resistant Gram-Negative Pathogens.

The rapid spread of superbugs leads to the escalation of infectious diseases, which threatens public health. Endolysins derived from bacteriophages are spotlighted as promising alternative antibiotics against multi-drug resistant bacteria. In this study, we isolated and characterized the novel Salmonella typhimurium phage PBST08. Bioinformatics analysis of the PBST08 genome revealed putative endolysin ST01 with a lysozyme-like domain. Since the lytic activity of the purified ST01 was minor, probably owing to the outer membrane, which blocks accessibility to peptidoglycan, antimicrobial peptide cecropin A (CecA) was fused to the N-terminus of ST01 to disrupt the outer membrane. The resulting CecA::ST01 has been shown to have increased bactericidal activity against gram-negative pathogens including Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumannii, Escherichia coli, and Enterobacter cloacae and the most affected target was A. baumannii. In the presence of 0.25 µM CecA::ST01, A. baumannii ATCC 17978 strain was completely killed and CCARM 12026 strain was wiped out by 0.5 µM CecA::ST01, which is a clinical isolate of A. baumannii and resistant to multiple drugs including carbapenem. Moreover, the larvae of Galleria mellonella could be rescued up to 58% or 49% by the administration of CecA::ST01 upon infection by A. baumannii 17978 or CCARM 12026 strain. Finally, the antibacterial activity of CecA::ST01 was verified using 31 strains of five gram-negative pathogens by evaluation of minimal inhibitory concentration. Thus, the results indicate that a fusion of antimicrobial peptide to endolysin can enhance antibacterial activity and the spectrum of endolysin where multi-drug resistant gram-negative pathogens can be efficiently controlled.

What is the link between endometriosis and adiposity?

Endometriosis is defined by the presence of extrauterine endometrial tissue and presents with symptoms of dysmenorrhea, chronic pelvic pain, and impaired fertility. This condition often follows a chronic progressive course with favorable recurrence, even after surgical or medical treatment. The etiology or exact pathophysiology of endometriosis remains to be clarified, although it is thought to be a complex and multifactorial disease. Prior epidemiological or population-based studies have reported several risk factors related to endometriosis, such as environmental, menstrual, habitual, and lifestyle factors. Moreover, anthropometry has been found to be significantly associated with the diagnosis of endometriosis, as a lower body mass index is associated with an elevated risk of endometriosis. Here, we review studies that have examined the association between body size and the risk of endometriosis and discuss the clinical and biological significance of the relationship between adiposity and endometriosis.

Meta-Analysis of Polymyositis and Dermatomyositis Microarray Data Reveals Novel Genetic Biomarkers.

Polymyositis (PM) and dermatomyositis (DM) are both classified as idiopathic inflammatory myopathies. They share a few common characteristics such as inflammation and muscle weakness. Previous studies have indicated that these diseases present aspects of an auto-immune disorder; however, their exact pathogenesis is still unclear. In this study, three gene expression datasets (PM: 7, DM: 50, Control: 13) available in public databases were used to conduct meta-analysis. We then conducted expression quantitative trait loci analysis to detect the variant sites that may contribute to the pathogenesis of PM and DM. Six-hundred differentially expressed genes were identified in the meta-analysis (false discovery rate (FDR) < 0.01), among which 317 genes were up-regulated and 283 were down-regulated in the disease group compared with those in the healthy control group. The up-regulated genes were significantly enriched in interferon-signaling pathways in protein secretion, and/or in unfolded-protein response. We detected 10 single nucleotide polymorphisms (SNPs) which could potentially play key roles in driving the PM and DM. Along with previously reported genes, we identified 4 novel genes and 10 SNP-variant regions which could be used as candidates for potential drug targets or biomarkers for PM and DM.

Antitumor therapeutic effects of a genetically engineered Salmonella typhimurium harboring TNF-α in mice.

Although the use of TNF-α in the treatment of cancer is restricted due to its non-specific cytotoxicity and narrow range of applications to different cancers in clinical trials, we investigated a safe anti-cancer drug by the use of engineered bacterial capsule harboring TNF-α. The engineered bacterial capsule was designed to target cancer cells, promote a tumor-suppressive environment, and increase the efficacy of existing cancer treatments, including chemotherapy, radiotherapy, and cell therapy. The engineered bacterial capsule was constructed with Salmonella capsulizing TNF-α protein, which was produced and capsulized by Salmonella to reduce side effects of the protein. This bacterial capsule induced a tumor-suppressive environment through the activation of natural killer cells. Engineered bacterial capsule invaded tumor cells, released TNF-α, and induced apoptosis of tumor cells without apparent side effects. In a murine melanoma model, the bacterial capsule of TNF-α significantly inhibited tumor growth by 80-100% and prolonged the survival of the mice. When tested in combination with chemotherapy (cisplatin), antibiotics, and vaccine, recombinant microbial treatment increased the anti-tumor effects of existing therapies. The anti-tumor effects of the bacterial capsule of TNF-α were also observed in cervical cancer, melanoma, breast cancer, colon cancer, and renal carcinoma. These results suggest that the bacterial capsule of TNF-α is a promising strategy for TNF-α treatment.

Comparison of antioxidant activity in wild plant (Adenophora triphylla) leaves and roots as a potential source of functional foods.

Adenophora triphylla is commonly used in food materials and oriental medicine as an analgesic, anti-inflammatory, and antitussive. In the present study, the leaves and roots of A. triphylla were extracted with water and ethanol, respectively, to examine the extracts' in vitro antioxidant activities and total phenolic contents, as well as A. triphylla's potential as a new functional food source and safe and inexpensive supply of antioxidants. Different antioxidant tests were employed and the results were compared with ascorbic acid as a standard antioxidant. The total extractable contents of phenolic compounds and flavonoids, which relate to antioxidant activity in medicinal plants, were also measured. The leaf extracts had notable levels of total phenolics and flavonoids and showed high radical and nitrite scavenging activities as well as inhibition activity against enzymes that induce oxidation. These results suggest that A. triphylla leaves are a potential ingredient for food supplements and a natural source of antioxidants.

Biological validation of plant-derived anti-human colorectal cancer monoclonal antibody CO17-1A.

We validated expression and biological activities of plant-derived monoclonal antibody (MAb(P)) CO17-1A for its efficacy in cancer immunotherapy. PCR and immunoblot analyses demonstrated insertion and expression of heavy and light chains of MAb CO17-1A in transgenic plants, respectively. Confocal analysis revealed that MAb(P) CO17-1A was accumulated throughout the cytoplasm near the outer membrane, suggesting its secretion to the outer membrane via a default pathway. Cell ELISA analysis confirmed that the MAb(P) CO17-1A heavy and light chains in crude plant leaf samples assembled to specifically bind SW948 human colorectal carcinoma cells. Flow cytometry analysis showed that the Fc domains of both the purified MAb(P) and the mammalian-derived MAb (MAb(M)) evidenced similar binding activity to the FcgammaRI receptor (CD64). The biological activities of both MAbs were similar, although the glycosylation pattern of MAb(P) CO17-1A is distinct from that of MAb(M). These results point to the potential use of MAb(P) CO17-1A for colorectal cancer immunotherapy.

Depressive symptoms in elementary school children in Jeju Island, Korea: prevalence and correlates.

We investigated the prevalence and correlates of depressive symptoms in elementary school children in Jeju Island, Korea. The study participants were 2305 children enrolled in elementary schools in Jeju-si, Seogwipo-si, Namjeju-gun, and Bukjeju-gun and their parents who completed questionnaires about sociodemographics, health habits, family relationship information, and the Korean form of the Kovac's children's depression inventory (CDI) in September to December 2005. Multiple logistic regression showed that higher age (OR = 1.259, 95% CI 1.098-1.445), short time spent developing a relationship with the mother (OR = 2.770, 95% CI 1.280-5.944), and a low level of body image satisfaction (OR = 3.397, 95% CI 1.823-6.330) were correlates of depressive symptoms in children. Our results suggest that the following are essential to prevent depressive symptoms in elementary school children in Jeju, Korea: advanced education and social activity programs at home, in school, and in the community to help children have a positive self-image, and much time spent building a relationship with the mother.