Depressed Neuronal Growth Associated Protein (GAP)-43 Expression in the Small Intestines of Mice Experimentally Infected with Neodiplostomum seoulense

Neodiplostomum seoulense (Digenea: Neodiplostomidae) is an intestinal trematode that can cause severe mucosal pathology in the small intestines of mice and even mortality of the infected mice within 28 days after infection. We observed neuronal growth associated protein-43 (GAP-43) expression in the myenteric plexus of the small intestinal wall of N. seoulense-infected mice until day 35 post-infection (PI). BALB/c mice were infected with 200 or 500 N. seoulense metacercariae isolated from naturally infected snakes and were killed every 7 days for immunohistochemical demonstration of GAP-43 in the small intestines. N. seoulense-infected mice showed remarkable dilatation of intestinal loops compared with control mice through days 7-28 PI. Conversely, GAP-43 expression in the mucosal myenteric plexus was markedly (P<0.05) reduced in the small intestines of N. seoulense-infected mice during days 7-28 PI and was slightly normalized at day 35 PI. From this study, it is evident that neuronal damage occurs in the intestinal mucosa of N. seoulense-infected mice. However, the correlation between intestinal pathology, including the loop dilatation, and depressed GAP-43 expression remains to be elucidated

Exploring aryl hydrocarbon receptor expression and distribution in the tumor microenvironment, with a focus on immune cells, in various solid cancer types

IntroductionAryl hydrocarbon receptor (AhR) is a transcription factor that performs various functions upon ligand activation. Several studies have explored the role of AhR expression in tumor progression and immune surveillance. Nevertheless, investigations on the distribution of AhR expression, specifically in cancer or immune cells in the tumor microenvironment (TME), remain limited. Examining the AhR expression and distribution in the TME is crucial for gaining insights into the mechanism of action of AhR-targeting anticancer agents and their potential as biomarkers.MethodsHere, we used multiplexed immunohistochemistry (mIHC) and image cytometry to investigate the AhR expression and distribution in 513 patient samples, of which 292 are patients with one of five solid cancer types. Additionally, we analyzed the nuclear and cytosolic distribution of AhR expression.ResultsOur findings reveal that AhR expression was primarily localized in cancer cells, followed by stromal T cells and macrophages. Furthermore, we observed a positive correlation between the nuclear and cytosolic expression of AhR, indicating that the expression of AhR as a biomarker is independent of its localization. Interestingly, the expression patterns of AhR were categorized into three clusters based on the cancer type, with high AhR expression levels being found in regulatory T cells (Tregs) in non-small cell lung cancer (NSCLC).DiscussionThese findings are anticipated to serve as pivotal evidence for the design of clinical trials and the analysis of the anticancer mechanisms of AhR-targeting therapies

Effects of the Simultaneous Application of Nonlinear Frequency Compression and Dichotic Hearing on the Speech Recognition of Severely Hearing-Impaired Subjects: Simulation Test

ObjectivesThe clinical effects of the simultaneous application of nonlinear frequency compression and dichotic hearing on people with hearing impairments have not been evaluated previously. In this study, the clinical effects of the simultaneous application of these two techniques on the recognition of consonant-vowel-consonant (CVC) words with fricatives were evaluated using normal-hearing subjects and a hearing loss simulator operated in the severe hearing loss setting.MethodsA total of 21 normal-hearing volunteers whose native language was English were recruited for this study, and two different hearing loss simulators, which were configured for severe hearing loss in the high-frequency range, were utilized. The subjects heard 82 English CVC words, and the word recognition score and response time were measured.ResultsThe experimental results demonstrated that the simultaneous application of these two techniques showed almost even performance compared to the sole application of nonlinear frequency compression in a severe hearing loss setting.ConclusionThough it is generally accepted that dichotic hearing can decrease the spectral masking thresholds of an hearing-impaired person, simultaneous application of the nonlinear frequency compression and dichotic hearing techniques did not significantly improve the recognition of words with fricatives compared to the sole application of nonlinear frequency compression in a severe hearing loss setting

Monolithic and Flexible Polyimide Film Microreactors for Organic Microchemical Applications Fabricated by Laser Ablation

Keeping limber: A monolithic and flexible polyimide film microreactor is introduced for organic reactions and syntheses. Unlike glass microreactors, it is easy to fabricate, yet it is inert to solvents and acids under harsh conditions, unlike other polymer microreactors

Sicyos angulatus ameliorates atherosclerosis through downregulation of aortic inflammatory responses in apolipoprotein E-deficient mice

Sicyos angulatus (SA), a summer annual vine originating from Northeastern USA, is a widely distributed noxious invasive plant. However, the clinical application of SA has not been investigated previously. The purpose of present study was to determine the effects of SA on atherosclerosis and its underlying mechanism. Atherosclerosis was induced by feeding apolipoprotein E-deficient (apoE(-/-)) mice with an atherogenic diet for 8 weeks. SA was administered daily by oral gavage during induction of atherosclerosis. ApoE(-/-) mice treated with SA demonstrated a significant reduction in atherosclerotic plaque area in the whole aorta and aortic sinus compared with vehicle-treated mice. The plasma lipid profiles, including triglyceride, total cholesterol, high-density lipoprotein and low-density lipoprotein, were not affected by SA administration. Of note, gene expression levels of proatherogenic cytokines including tumor necrosis factor alpha (Tnf alpha) and interleukin-6 (Il-6) were significantly decreased in the aorta of SA administered apoE(-/-) mice. In lipopolysaccharide-stimulated RAW 264.7 macrophage cells, SA also inhibited the induction Tnfa, Il-6 and Il-1 beta in a dose-dependent manner. Furthermore, gene expression levels of endothelial cell adhesion molecules, including vascular cell adhesion protein 1 and intercellular adhesion molecule 1 were reduced in the aorta of apoE(-/-) mice treated with SA, which was followed by diminished aortic infiltration of monocytes/macrophages. In conclusion, to the best of our knowledge, this is the first study to demonstrate that SA is able to suppress the development of atherosclerosis by inhibiting the aortic expression of proinflammatory factors in atherogenic diet-fed apoE(-/-) mice. The present study may provide novel insights into the application of the environmentally problematic weed SA as a therapeutically effective natural product for preventing atherosclerosis.N

YH29407 with anti-PD-1 ameliorates anti-tumor effects via increased T cell functionality and antigen presenting machinery in the tumor microenvironment

Among cancer cells, indoleamine 2, 3-dioxygenase1 (IDO1) activity has been implicated in improving the proliferation and growth of cancer cells and suppressing immune cell activity. IDO1 is also responsible for the catabolism of tryptophan to kynurenine. Depletion of tryptophan and an increase in kynurenine exert important immunosuppressive functions by activating regulatory T cells and suppressing CD8+ T and natural killer (NK) cells. In this study, we compared the anti-tumor effects of YH29407, the best-in-class IDO1 inhibitor with improved pharmacodynamics and pharmacokinetics, with first and second-generation IDO1 inhibitors (epacadostat and BMS-986205, respectively). YH29407 treatment alone and anti-PD-1 (aPD-1) combination treatment induced significant tumor suppression compared with competing drugs. In particular, combination treatment showed the best anti-tumor effects, with most tumors reduced and complete responses. Our observations suggest that improved anti-tumor effects were caused by an increase in T cell infiltration and activity after YH29407 treatment. Notably, an immune depletion assay confirmed that YH29407 is closely related to CD8+ T cells. RNA-seq results showed that treatment with YH29407 increased the expression of genes involved in T cell function and antigen presentation in tumors expressing ZAP70, LCK, NFATC2, B2M, and MYD88 genes. Our results suggest that an IDO1 inhibitor, YH29407, has enhanced PK/PD compared to previous IDO1 inhibitors by causing a change in the population of CD8+ T cells including infiltrating T cells into the tumor. Ultimately, YH29407 overcame the limitations of the competing drugs and displayed potential as an immunotherapy strategy in combination with aPD-1

Urachal Actinomycosis Mimicking a Urachal Tumor

A 26-year-old man presented with lower abdominal discomfort and a palpable mass in the right lower quadrant. An abdominal computed tomography (CT) scan revealed an abdominal wall mass that extended from the dome of the bladder. Fluorine-18 fluorodeoxyglucose (FDG) positron-emission tomography/CT (PET/CT) showed hypermetabolic wall thickening around the bladder dome area that extended to the abdominal wall and hypermetabolic mesenteric infiltration. Differential diagnosis included a urachal tumor with invasion into adjacent organs and chronic inflammatory disease. Partial cystectomy with abdominal wall mass excision was performed, and the final pathologic report was consistent with urachal actinomycosis

Humulus japonicus attenuates LPS-and scopolamine-induced cognitive impairment in mice

Background : Neuroinflammation plays an important role in cognitive decline and memory impairment in neurodegenerative disorders. Previously, we demonstrated that Humulus japonicus (HJ) has anti-inflammatory effects in rodent models of Alzheimer’s disease and Parkinson’s disease. The present study aimed to examine the protective potential of HJ extracts against lipopolysaccharide (LPS)-induced cognitive impairment and scopolamine-induced amnesia in mouse models. Cognitive improvement of mice was investigated by novel object recognition test. For analyzing effects on neuroinflammation, immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR) assays were performed. Results : We found that the oral administration of HJ significantly improved cognitive dysfunction induced by LPS in a novel object recognition test. The LPS-induced activation of microglia was notably decreased by HJ treatment in the cortex and hippocampus. HJ administration with LPS also significantly increased the mRNA expression of interleukin (IL)-10 and decreased the mRNA expression of IL-12 in the parietal cortex of mice. The increased expression of LPS-induced complement C1q B chain (C1bq) and triggering receptor expressed on myeloid cells 2 (Trem2) genes was significantly suppressed by HJ treatment. In addition, HJ administration significantly improved novel object recognition in a scopolamine-induced amnesia mouse model. Conclusions : These findings revealed that HJ has a beneficial effect on cognitive impairment and neuroinflammation induced by systemic inflammation and on amnesia induced by scopolamine in mice.This study was supported by the KRIBB Research Initiative Program of the Republic of Korea (KGS1042221) and the Development of Platform Technology for Innovative Medical Measurements funded by Korea Research Institute of Standards and Science (KRISS-GP2022-2)

Prevalence of Otolaryngologic Diseases in South Korea: Data from the Korea National Health and Nutrition Examination Survey 2008

Objectives. The aims of this study were to evaluate the prevalence of otolaryngologic diseases in Korea. Methods. We obtained data from the 2008 Korea National Health and Nutrition Examination Surveys (KNHANES), which were cross-sectional surveys of the civilian, non-institutionalized population of South Korea (n=4,930). A field survey team that included an otolaryngologist, nurses, and interviewers moved with a mobile examination unit and performed otolaryngologic interviews and physical examinations. Results. The prevalence of subjective hearing loss, tinnitus, preauricular fistua, tympanic membrane perforation, and cholesteatoma were 11.97%, 20.27%, 2.08%, 1.60%, and 1.18%, respectively. Dizziness and vestibular dysfunction were common among Korean adults, since 23.33% of the participants reported symptoms of dizziness or imbalance, and the prevalence of vestibular dysfunction was 3.86%. The prevalence of nasal diseases was relatively high, as the prevalence of allergic rhinitis, chronic rhinosinusitis, and a deviated nasal septum were 28.01%, 7.12%, and 42.94%, respectively. Subjective dysphonia was found in 6.60% of the participants, and the prevalence of subjective dysphonia increased with age. Conclusion. This is the first nation-wide epidemiologic study to assess the prevalence of otolaryngologic diseases by both the Korean Otolaryngologic Society and the Ministry of Health and Welfare. Considering the high prevalence of otolaryngologic diseases in Korea, the results call for additional studies to better prevent and manage otolaryngologic diseases