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1.
Biomolecules ; 14(3)2024 Mar 18.
Article En | MEDLINE | ID: mdl-38540778

INTRODUCTION: Eosinophils contribute to the pathogenesis of allergic diseases, including asthma, allergic rhinitis, and atopic dermatitis. We previously reported that human tissue eosinophils have high CD69 expression compared to blood eosinophils, and its expression is correlated with disease severity and the number of infiltrated eosinophils. However, biological CD69 signaling activity in eosinophils remains unclear. METHODS: CD69 expression on lung tissue eosinophils obtained from mice with ovalbumin-induced asthma was measured using flow cytometry. CD69 crosslinking was performed on eosinophils purified from the spleen of IL-5 transgenic mice to investigate CD69 signaling and its function in eosinophils. Then, qPCR, Western blot, enzyme-linked immunosorbent assay, and survival assay results were analyzed. RESULTS: Surface CD69 expression on lung tissue eosinophils in the asthma mice model was 2.91% ± 0.76%, whereas no expression was detected in the healthy group. CD69-expressed eosinophils intrinsically have an upregulation of IL-10 mRNA expression. Moreover, CD69 crosslinking induced further pronounced IL-10 production and apoptosis; these responses were mediated via the Erk1/2 and JNK pathways, respectively. CONCLUSIONS: Our results suggested that CD69+ eosinophils play an immunoregulator role in type 2 inflammation, whereas activated tissue eosinophils contribute to the pathogenesis of asthma.


Asthma , Eosinophils , Animals , Humans , Mice , Antigens, CD/metabolism , Apoptosis , Asthma/metabolism , Eosinophils/metabolism , Interleukin-10/genetics , Interleukin-10/metabolism , MAP Kinase Signaling System
2.
World Neurosurg ; 185: e944-e950, 2024 May.
Article En | MEDLINE | ID: mdl-38458249

BACKGROUND: Cytotoxic lesions of the corpus callosum (CLOCCs) are occasionally associated with aneurysmal subarachnoid hemorrhage (aSAH). The effects of aSAH on clinical outcomes in such cases are unclear. The present study aimed to investigate the frequency and characteristics of CLOCCs associated with aSAH to ascertain the predictors of shunt-dependent chronic hydrocephalus (SDCH) after aSAH. METHODS: We retrospectively investigated cases of aSAH treated by coil embolization. Patients were divided into those with and without CLOCCs. Between-group differences were evaluated, including clinical outcomes and the characteristics of both the patients and the aneurysms. Patients were divided into those with and without SDCH to identify predictive factors of SDCH after aSAH focusing on CLOCCs. RESULTS: This single-center study included 196 patients with aSAH. All patients received coil embolization between April 2013 and March 2020. CLOCCs were detected in 38 (19.4%) patients. In the group with CLOCCs, male sex, poor severity grade at onset, acute hydrocephalus, SDCH (all P < 0.01), and Fisher group 3 or 4 (P = 0.04) were significantly more common than in the group without CLOCCs. Diabetes and CLOCCs were significant predictors of SDCH after aSAH in multivariate analysis (diabetes: P < 0.01, odds ratio: 6.73, 95% confidence interval: 1.61-28.09; CLOCCs: P < 0.01, odds ratio: 6.86, 95% confidence interval: 2.87-16.38). CONCLUSIONS: CLOCCs and SDCH were common in patients with poor-grade aSAH, and CLOCCs were independent predictors of SDCH after aSAH. Meticulous follow-up is necessary to detect SDCH after aSAH, especially in patients with poor-grade aSAH and CLOCCs.


Corpus Callosum , Embolization, Therapeutic , Hydrocephalus , Subarachnoid Hemorrhage , Humans , Male , Hydrocephalus/etiology , Hydrocephalus/surgery , Female , Subarachnoid Hemorrhage/surgery , Subarachnoid Hemorrhage/complications , Subarachnoid Hemorrhage/diagnostic imaging , Middle Aged , Corpus Callosum/diagnostic imaging , Retrospective Studies , Aged , Embolization, Therapeutic/methods , Adult , Chronic Disease , Cerebrospinal Fluid Shunts
4.
J Neuroendovasc Ther ; 18(2): 29-36, 2024.
Article En | MEDLINE | ID: mdl-38384393

Objective: Intraoperative rebleeding during endovascular treatment for ruptured intracranial aneurysms is associated with poor prognosis. Lumbar drainage is performed preoperatively to control intracranial pressure; however, it is associated with a risk of brain herniation or rebleeding because intracranial pressure may change rapidly. Therefore, this study aimed to examine the efficacy and safety of preoperative lumbar drainage. Methods: This retrospective study enrolled 375 patients who underwent endovascular treatment of ruptured intracranial aneurysms at our institution between April 2013 and March 2018. The incidence of rebleeding and clinical outcomes were compared between patients who did and did not undergo preoperative lumbar drainage. Results: Among the 375 patients with ruptured intracranial aneurysms, 324 (86.0%) and 51 (14.0%) patients did and did not undergo lumbar drainage, respectively. The incidence of rebleeding was 11/324 (3.4%) and 2/51 (3.9%) in lumbar drainage and nonlumbar drainage groups, respectively, with no statistical differences (p = 0.98). Of the rebleeding cases, 9/11 (81%) and 2/2 (100%) in lumbar drainage and nonlumbar drainage groups, respectively, were due to intraoperative bleeding, and 2/11 (19%) in the lumbar drainage group, the causes of the rebleeding were undetermined. The incidence of symptomatic vasospasm did not differ significantly between the groups (13.2% vs. 11.8%, P = 0.776), while the incidence of hydrocephalus (24.6% vs. 11.8%, P = 0.043) and meningitis (15.2% vs. 5.9%, P = 0.075) were slightly higher in the lumbar drainage group. Favorable clinical outcomes (modified Rankin Scale score <2) at discharge were less frequent in the lumbar drainage group (55.3% vs. 70.0%, P = 0.051). No significant differences were observed in the propensity score-matched analysis. Conclusion: Lumbar drainage before endovascular treatment for ruptured intracranial aneurysms is a safe procedure that does not increase the incidence of rebleeding.

5.
World Neurosurg X ; 21: 100265, 2024 Jan.
Article En | MEDLINE | ID: mdl-38173683

Background: Aneurysm size is considered a risk factor for aneurysm rupture, and even small aneurysms may rupture, especially bifurcation aneurysms (BAs), which are occasionally detected. Therefore, we aimed to investigate the predictors of retreatment after coil embolization for unruptured BAs, with a particular focus on the absolute and relative size of the aneurysm (size ratio [SR]). Methods: To evaluate the predictors of retreatment, patients were divided into two groups: those with and those without retreatment. Patient characteristics and radiographic assessments were compared between the groups. SR was defined as the ratio of the maximum aneurysm diameter and the average diameter of the parent artery. Results: Overall, 181 unruptured BAs in 176 patients were investigated. The mean age of the patients was 63.8 ± 9.6 years. The mean aneurysm size and SR were 7.18 ± 2.94 mm and 2.49 ± 1.32, respectively. Further, 12 aneurysms with retreatment (6.6 %) and 169 aneurysms without retreatment were compared. In univariate analysis, SR was significantly higher in the group with retreatment (P = 0.02), but aneurysm size was not significantly different between the groups (P = 0.09). Multivariable analysis revealed that SR > 2.6 was a significant predictor of retreatment (P = 0.03; odds ratio: 10.41; 95 % confidence interval: 2.1-51.73). Conclusions: This study showed that SR influences retreatment after coil embolization for unruptured BAs. Therefore, if the aneurysm size and parent artery diameter were small, as in cases with a large SR, meticulous follow-up after coil embolization is required to detect recurrence and recanalization.

6.
J Nippon Med Sch ; 91(1): 99-107, 2024 Mar 09.
Article En | MEDLINE | ID: mdl-38072419

BACKGROUND: Repeated triage training is necessary to maintain and improve the accuracy of simple triage and rapid treatment (START), a popular triage method. Virtual reality (VR) may be more effective than conventional training methods. This study aimed to verify the educational usefulness of START using VR originally developed for students. METHODS: A VR was initially developed with a function that allowed students to select the triage procedure and its evaluation. Triage was performed using a simple modified START method, and eight scenarios were developed. The participants included 70 paramedic students classified into VR and live lecture groups. They took a 20-question written test that evaluated their academic ability before the course. After the course, a practical test and a 20-question written test were conducted. The total score of the practical test was 43 points. Triage procedure (1 point), observation and evaluation (1-5 points), and triage categories (1 point) were evaluated in this test. RESULTS: The VR and live lecture groups consisted of 33 and 29 participants, respectively. No significant differences were observed pre- and post-test. In the practical test, the median (interquartile range) score was 29 (26-32) and 25 (23-29) for the VR and live lecture groups, respectively, with the VR group scoring significantly higher (P=0.03). CONCLUSION: Our results confirmed the educational usefulness of selective VR for active learning of START. Therefore, VR combined with live lectures and simulations would be an optimal educational technique.


Mass Casualty Incidents , Virtual Reality , Humans , Triage/methods , Clinical Competence , Students
7.
J Obstet Gynaecol Res ; 50(3): 351-357, 2024 Mar.
Article En | MEDLINE | ID: mdl-38072834

AIM: We aimed to investigate the associations of endometriosis and adenomyosis with pregnancy complications by using a large-scale Japanese database. METHODS: We retrospectively analyzed 145 590 singleton pregnancies from the Japan Perinatal Registry Network Database. Pregnant women registered as having endometriosis or adenomyosis were designated as the case group (EA), whereas the control group (non-EA) was selected using propensity-score matching adjusted for variables such as age, parity, BMI, smoking history, and the use of assisted reproductive technology. The main outcomes included placental malposition, preterm birth, and hypertensive disorders of pregnancy (HDP). RESULTS: In total, 1203 patients from both the EA and non-EA groups were matched and evaluated. The EA group showed significantly higher rates of placenta previa (odds ratio [OR], 3.01; 95% confidence interval [CI], 1.84-4.92), low-lying placenta (OR, 2.02; 95% CI, 1.06-3.86), and preterm birth (OR, 1.44; 95% CI, 1.13-1.84) than the non-EA group. However, no significant difference was observed in the incidence of HDP (OR, 1.22; 95% CI, 0.90-1.66). CONCLUSION: The use of propensity-score matching to analyze a nationwide perinatal database in Japan clarified that EA was associated with increased pregnancy complications, specifically placental malposition, including placenta previa and low-lying placenta, and preterm birth, but not with HDP.


Adenomyosis , Endometriosis , Placenta Previa , Pre-Eclampsia , Pregnancy Complications , Premature Birth , Pregnancy , Female , Humans , Infant, Newborn , Endometriosis/complications , Endometriosis/epidemiology , Placenta Previa/epidemiology , Premature Birth/epidemiology , Premature Birth/etiology , Adenomyosis/complications , Pregnant Women , Japan/epidemiology , Retrospective Studies , Placenta , Pregnancy Complications/epidemiology , Pre-Eclampsia/etiology
8.
Clin J Gastroenterol ; 17(1): 80-83, 2024 Feb.
Article En | MEDLINE | ID: mdl-37919638

Well-differentiated neuroendocrine tumor, Grade 1 (NET, G1), in the hypopharynx is extremely rare. A 62-year-old woman was referred to our clinic with a tumor in the postcricoid area. The tumor was diagnosed NET on biopsy and there were no metastatic findings on CT, therefore we performed endoscopic resection. Histologic examination revealed well-differentiated neuroendocrine tumor, Grade 1. This case was an extremely rare and valuable case in which endoscopic images can be observed in detail. Endoscopic resection was performed and successful endoscopic and histological resection was achieved.


Neuroendocrine Tumors , Female , Humans , Middle Aged , Neuroendocrine Tumors/diagnostic imaging , Neuroendocrine Tumors/surgery , Hypopharynx/diagnostic imaging , Hypopharynx/surgery , Hypopharynx/pathology , Endoscopy , Biopsy
9.
Cells ; 12(23)2023 11 30.
Article En | MEDLINE | ID: mdl-38067174

Eosinophilic airway inflammation, complicated by bronchial asthma and eosinophilic chronic rhinosinusitis (ECRS), is difficult to treat. The disease may become refractory when eosinophilic mucin associated with eosinophil peroxidase (EPX) and autoantibodies fills in the paranasal sinus and small airway. This study investigated the functional role of an anti-EPX antibody in eosinophilic mucin of ECRS in eosinophilic airway inflammation. Eosinophilic mucin was obtained from patients with ECRS. The effects of the anti-EPX antibody on dsDNA release from eosinophils and eosinophilic mucin decomposition were evaluated. Immunofluorescence or enzyme-linked immunosorbent assays were performed to detect the anti-EPX antibody and its supernatant and serum levels in eosinophilic mucin, respectively. The serum levels of the anti-EPX antibody were positively correlated with sinus computed tomography score and fractionated exhaled nitrogen oxide. Patients with refractory ECRS had higher serum levels of the anti-EPX antibody than those without. However, dupilumab treatment decreased the serum levels of the anti-EPX antibody. Immunoglobulins (Igs) in the immunoprecipitate of mucin supernatants enhanced dsDNA release from eosinophils, whereas the neutralization of Igs against EPX stopped dsDNA release. Furthermore, EPX antibody neutralization accelerated mucin decomposition and restored corticosteroid sensitivity. Taken together, the anti-EPX antibody may be involved in the formulation of eosinophilic mucin and be used as a clinical marker and therapeutic target for intractable eosinophilic airway inflammation.


Eosinophil Peroxidase , Eosinophilia , Mucins , Sinusitis , Humans , Antibodies , Eosinophil Peroxidase/immunology , Eosinophilia/drug therapy , Eosinophils , Inflammation , Mucins/metabolism , Sinusitis/drug therapy
10.
Pathol Res Pract ; 252: 154943, 2023 Dec.
Article En | MEDLINE | ID: mdl-37977036

The nucleic acid integrity of head and neck squamous cell carcinoma (HNSCC) samples is poor, and the material available for genetic analysis is limited. Therefore, to expand the effectiveness of personalized medicine in patients with HNSCC, a new sampling method is needed. In total, 128 samples from 44 patients with HNSCC were studied: 32 genetic analysis samples (GASs) collected as 5 × 5 × 5 mm tissue fragments from resected large tumors and immediately embedded in a small formalin bottle within 10 min (i.e., the ischemic time), 43 primary tumor components (primary), 14 decalcified tumor (DC) samples, 32 metastatic tumors in lymph nodes (LNs), and 7 parakeratinized components (PKCs). The nucleic acid quality in the GAS, primary, DC, LN, and PKC groups was compared and next-generation sequencing (NGS) was performed. DNA integrity number and percentage of RNA fragments with > 200 nucleotides were significantly higher in the GAS group than those in the other groups. RNA integrity number decreased first in LN, followed by GAS, primary, and DC. No significant differences were observed in DIN, RIN and DV200 among the PKC, primary and LN. Following methyl green-pyronin staining, preserved DNA and RNA were not visualized in DC samples. Most NGS metrics did not differ significantly among primary, LN, and PKC samples. In conclusion, GASs should be collected during routine hospital activities. When the volume of viable materials is limited, PKCs should be considered for genetic analysis.


Head and Neck Neoplasms , Nucleic Acids , Humans , Squamous Cell Carcinoma of Head and Neck/genetics , Retrospective Studies , Head and Neck Neoplasms/genetics , Head and Neck Neoplasms/surgery , DNA , Specimen Handling , RNA
11.
World Neurosurg ; 180: e716-e728, 2023 Dec.
Article En | MEDLINE | ID: mdl-37821031

OBJECTIVE: We investigated the association between the inflow angle of aneurysms and their occlusion status at 1 and 2 years after flow diverter (FD) treatment. METHODS: We retrospectively analyzed 42 consecutive patients from a single center with 43 untreated, unruptured internal carotid artery (ICA) proximal to communicating segment, saccular aneurysms sized <12 mm. RESULTS: At 1 year posttreatment, the complete occlusion (CO) rate was 58.1%. On univariate analyses, the proportion of inflow angle >90° was significantly lower in the CO group than in the incomplete occlusion group (20.0% VS. 83.3%; P < 0.001). The CO incidence decreased with a height-width (H/W) ratio of <1.2 (P = 0.059). On multivariate analysis, an H/W ratio of <1.2 (odds ratio [OR], 0.076; P = 0.027) and an inflow angle of >90° (OR, 0.020; P = 0.0011) significantly influenced CO at 1 year post FD. At 2 years posttreatment, the CO rate was 76.3% (29/38 cases with available follow-up data). On univariate analyses, in the CO group compared to the incomplete occlusion group, the proportion of H/W ratio <1.2 was significantly lower (P = 0.005) and the proportion of inflow angle >90° was significantly lower (P = 0.021); aneurysm dome size tended to be larger (8.5 mm vs. 7.1 mm; P = 0.080). On multivariate analysis, an H/W ratio <1.2 (OR, 0.042; P = 0.015) and an inflow angle >90° (OR: 0.088; P = 0.031) significantly influenced CO at 2 years post FD. CONCLUSIONS: The inflow angle of >90° and H/W ratio <1.2 may significantly influence the CO rate in small- or medium-sized internal carotid artery aneurysms 1 and 2 years post FD.


Carotid Artery Diseases , Embolization, Therapeutic , Endovascular Procedures , Intracranial Aneurysm , Humans , Intracranial Aneurysm/diagnostic imaging , Intracranial Aneurysm/surgery , Retrospective Studies , Carotid Artery, Internal/diagnostic imaging , Carotid Artery, Internal/surgery , Carotid Artery Diseases/diagnostic imaging , Carotid Artery Diseases/surgery , Treatment Outcome , Stents
12.
AJOG Glob Rep ; 3(4): 100265, 2023 Nov.
Article En | MEDLINE | ID: mdl-37771974

BACKGROUND: Adenomyosis is associated with unfavorable perinatal outcomes; however, the effect of an adenomyomectomy on pregnancy outcomes remains unclear. Pregnancy following an adenomyomectomy has been reported to be associated with a high risk for uterine rupture; however, the actual incidence remains unknown. OBJECTIVE: This study aimed to evaluate the effect of an adenomyomectomy on pregnancy outcomes by retrospectively comparing the pregnancy outcomes of women who underwent an adenomyomectomy with those of women with adenomyosis. STUDY DESIGN: This was a single-center retrospective study in which the pregnancy outcomes of women who underwent an adenomyomectomy and for whom complete resection of the affected tissue under laparotomy was achieved were compared with those of women with adenomyosis. The following pregnancy outcomes were examined: second-trimester miscarriage, preterm prelabor rupture of membranes, preterm delivery, spontaneous preterm delivery, preeclampsia, rate of cesarean delivery, blood loss during cesarean delivery, incidence of placenta accreta spectrum, neonatal body weight, and small for gestational age infants. RESULTS: A total of 18 pregnant women who underwent an adenomyomectomy and 105 pregnant women with adenomyosis were included in this study. All women who underwent an adenomyomectomy delivered via cesarean delivery, and among them, 1 had a uterine rupture at 30 weeks of gestation. Although there was no significant difference between pregnant women who underwent an adenomyomectomy and those with adenomyosis in the incidence of second-trimester miscarriage (0% [0/18] vs 7.6% [8/105], respectively; P=.22), preterm delivery (50% [9/18] vs 32% [34/105], respectively; P=.15), and spontaneous preterm delivery (6% [1/18] vs 15% [16/105], respectively; P=.26), a significant decrease in preterm prelabor rupture of membrane (0% [0/18] vs 12% [13/105], respectively; P<.05), preeclampsia (0% [0/18] vs 12% [13/105], respectively; P<.05), and small for gestational infants (0% [0/18] vs 15% [16/105], respectively; P<.05), as well as a significant increase in the incidence of placenta accreta spectrum (50% [9/18] vs 0% [0/105], respectively; P<.01) and blood loss during cesarean delivery (1748 mL vs 1330 mL, respectively; P<.05) were observed. CONCLUSION: Uterine rupture following an adenomyomectomy may occur because of the high incidence of placenta accreta spectrum. However, an adenomyomectomy may reduce adverse pregnancy outcomes associated with adenomyosis, such as preterm prelabor rupture of membranes, preeclampsia, and small for gestational age infants. An adenomyomectomy may be a viable option for women among whom the procedure is inevitable before conception.

13.
Opt Express ; 31(18): 29954-29967, 2023 Aug 28.
Article En | MEDLINE | ID: mdl-37710784

Polarized optical microscopy (POM) images of polymer network liquid crystals (PNLCs) were first analyzed using a pretrained machine learning model for feature extraction and hierarchical clustering. The analyses worked well in predicting and improving the thermoresponsive changes individually in direct luminous and hemispheric solar transmittance, both of which are crucial properties of energy-saving smart windows. The features of a 1280 × 1920-pixel color POM image were extracted by the latest pretrained algorithm, EfficientNet-B7, as a 2560-dimensional vector and then reduced into a two-dimensional space for clustering and visualization using the uniform manifold approximation and projection (UMAP) algorithm while efficiently preserving the global structures of the distance relationship in a high-dimensional space. The feature vectors in the UMAP space were correlated with the thermoresponsive transmittance and classified using hierarchical clustering analysis. The extracted features belonging to some clusters were also correlated with the fabrication parameters. The PNLCs here were produced from various raw materials under different fabrication conditions. These analyses and predictability are extensively applied to different PNLCs for stimuli-responsive optical devices, such as solar- and privacy-control windows.

14.
J Neuroendovasc Ther ; 17(7): 132-138, 2023.
Article En | MEDLINE | ID: mdl-37546345

Objective: The flow diverter (FD) is a promising device. Apart from two main complications, hemorrhagic and ischemic ones, stent migration is reportedly an unusual complication. In particular, distal migration of the FD has rarely been reported. We report a case of asymptomatic acute distal migration of the flow-redirection endoluminal device (FRED). Case Presentation: A 50-year-old woman was incidentally diagnosed with an unruptured right internal carotid-ophthalmic artery aneurysm with a maximum diameter of 8.0 mm, and she subsequently underwent endovascular treatment with FRED. Based on the vessel diameter (3.8 mm proximal and 3.6 mm distal to the aneurysm), a 4.0-mm-diameter and 18-mm-long FRED was deployed without postoperative complications. However, on MRA 12 months after treatment, the aneurysm was not occluded; angiography showed distal migration of the FRED. The postoperative MRA and skull X-ray images were retrospectively reviewed to determine the period of the migration. The skull X-ray images and the signal loss area due to the FRED on MRA 1 day after the treatment had already demonstrated the migration of the FRED. In the second treatment, a 4.0-mm-diameter and 23-mm-long FRED was deployed in an overlapping fashion up to the proximal part of the carotid siphon. Prompt identification of distal migration of the FD without neurologic signs could be challenging. Conclusion: It is important to follow up meticulously with MRA and skull X-ray images after FD treatment for detecting stent migrations as early as possible.

15.
Case Rep Oncol ; 16(1): 465-473, 2023.
Article En | MEDLINE | ID: mdl-37485015

Solitary fibrous tumors (SFTs) are soft tumors (mesenchymal origin) that most likely develop from adult mesenchymal stem cells. SFTs are not common in the head and neck region, and the characteristics of tumors in this location are unclear. The present study describes the clinicopathological findings of 2 cases of SFTs arising in the parotid gland and buccal space, presenting as salivary gland tumors. The first case is a 76-year-old man presenting with a painless tumor on the right parotid gland who subsequently underwent partial superficial parotidectomy. According to the results of histopathological analysis, the tumor consisted of stellate and spindle-shaped cells proliferating on a mucous-like substrate. Immunohistochemical staining revealed that neoplastic cells were positive for CD34, vimentin, Bcl2, and STAT6. The second case is of a 64-year-old man presenting with a painless lump on his right cheek. Based on the findings of fine needle aspiration cytology, a tumor derived from myoepithelial cells of the minor salivary gland or a nonepithelial tumor was suspected. The patient underwent surgical resection via an intraoral approach. Histopathologically, the tumor consisted of spindle-shaped cells with rod-shaped or irregular nuclei. Immunohistochemical staining revealed that the neoplastic cells were positive for CD34, CD99, Bcl2, and STAT6. Briefly, SFT should be considered in the differential diagnosis of a well-marginalized lesion in the salivary gland and oral cavity. STAT6 immunohistochemistry is the most specific and sensitive method of diagnosing SFT. A thorough understanding of the morphological changes associated with SFT and their correlation with clinical, immunohistochemical, and molecular characteristics is important to avoid misdiagnosis.

16.
JCI Insight ; 8(14)2023 07 24.
Article En | MEDLINE | ID: mdl-37318881

The RNA-binding protein LIN28B is overexpressed in over 30% of patients with colorectal cancer (CRC) and is associated with poor prognosis. In the present study, we unraveled a potentially novel mechanism by which LIN28B regulates colonic epithelial cell-cell junctions and CRC metastasis. Using human CRC cells (DLD-1, Caco-2, and LoVo) with either knockdown or overexpression of LIN28B, we identified claudin 1 (CLDN1) tight junction protein as a direct downstream target and effector of LIN28B. RNA immunoprecipitation revealed that LIN28B directly binds to and posttranscriptionally regulates CLDN1 mRNA. Furthermore, using in vitro assays and a potentially novel murine model of metastatic CRC, we show that LIN28B-mediated CLDN1 expression enhances collective invasion, cell migration, and metastatic liver tumor formation. Bulk RNA sequencing of the metastatic liver tumors identified NOTCH3 as a downstream effector of the LIN28B/CLDN1 axis. Additionally, genetic and pharmacologic manipulation of NOTCH3 signaling revealed that NOTCH3 was necessary for invasion and metastatic liver tumor formation. In summary, our results suggest that LIN28B promotes invasion and liver metastasis of CRC by posttranscriptionally regulating CLDN1 and activating NOTCH3 signaling. This discovery offers a promising new therapeutic option for metastatic CRC to the liver, an area where therapeutic advancements have been relatively scarce.


Colonic Neoplasms , Colorectal Neoplasms , Liver Neoplasms , Humans , Animals , Mice , Colorectal Neoplasms/pathology , Claudin-1/genetics , Claudin-1/metabolism , Caco-2 Cells , Liver Neoplasms/genetics , Receptor, Notch3/metabolism , RNA-Binding Proteins/genetics
17.
Mol Clin Oncol ; 18(5): 38, 2023 May.
Article En | MEDLINE | ID: mdl-37035471

Immune checkpoint inhibitor (ICI) therapy has been less effective in patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations than in patients with EGFR wild-type NSCLC. This retrospective study was conducted to investigate the associations of clinical parameters with the efficacy of ICI therapy in patients with EGFR-mutant NSCLC. Clinical information was retrieved from the medical charts, and immunohistochemical analysis was performed in some cases to determine the tumor-infiltrating CD68-positive cell count. Data from 46 patients were included in the analysis. The median (95% confidence interval) progression-free survival and overall survival from the initiation of ICI therapy was 1.4 months (1.0-1.7 months) and 6.4 months (3.9-19.0 months), respectively. Analysis using a Cox proportional hazards model revealed that tumor programmed death-ligand 1 expression was associated with the overall survival of patients with EGFR-mutant NSCLC after ICI treatment. The tumor-infiltrating CD68-positive cell count was evaluated in 11 patients. Comparison using the log-rank test revealed that the progression-free survival time after ICI treatment was longer in the patients with lower tumor-infiltrating CD68-positive cell counts than those with higher tumor-infiltrating CD68-positive cell counts. The present analysis demonstrated that PD-L1 expression and the tumor-infiltrating CD68-positive cell count may be associated with the efficacy of ICI therapy in patients with NSCLC harboring EGFR mutations.

18.
Exp Gerontol ; 177: 112184, 2023 06 15.
Article En | MEDLINE | ID: mdl-37105504

Despite the increase in age-related hearing loss (ARHL) prevalence owing to increased population aging, preventive measures against ARHL have not yet been established. The immune system becomes one of the most dysfunctional systems upon aging, and immunosenescence greatly affects homeostasis and promotes systemic aging along with chronic inflammation and oxidative stress. This study aimed to determine whether immuno-rejuvenation procedures can prevent ARHL and have clinical applications as well as to analyze the communication mechanisms between the systemic immune system and the cochlea using a murine model. Lymphocytes from young mice inhibited the progression of ARHL. The method of cryopreserving these lymphocytes and inoculating them at the onset of ARHL suggests their clinical application. Mice that were administered this treatment not only maintained auditory threshold but also avoided spinal ganglion degeneration, cellular immune aging, and nitric oxide production, which causes age-related tissue damage. These findings coincide with our previous strategies against immunosenescence and neuronal aging. Therefore, the manipulation of systemic immune function may contribute not only to the prevention of ARHL but also to the development of novel anti-aging clinical measures, paving the way to healthy longevity with preserved organ function.


Presbycusis , Animals , Mice , Disease Models, Animal , Presbycusis/prevention & control , Cochlea , Aging/physiology , Lymphocytes
19.
Clin Neurol Neurosurg ; 228: 107699, 2023 05.
Article En | MEDLINE | ID: mdl-37023486

PURPOSE: Coil embolization is one of the main endovascular treatment for basilar apex aneurysms (BAAs), and thromboembolic events are important complications of coil embolization. Even in small aneurysms, there is a risk of rupture, and aggressive treatment should be considered for unruptured BAAs. Using diffusion-weighted imaging (DWI), the study aimed to investigate thromboembolic events after coil embolization for unruptured BAAs by focusing on the absolute aneurysm size and relative aneurysm size (size ratio [SR]). METHODS: To evaluate the predictors of thromboembolic events, patients were divided into those with and without hyperintensity on DWI after coil embolization. Patient and radiographic characteristics were compared between the two groups. SR was defined as the maximum aneurysm diameter divided by the average parent artery diameter. RESULTS: Fifty-six unruptured BAAs in 56 patients were investigated. The mean aneurysm size and SR were 7.61 ± 2.18 mm and 2.74 ± 1.45, respectively. Postprocedural hyperintensity on DWI was detected in 17 patients (30.4%). SR was significantly larger in the group with hyperintensity on DWI (3.75 ± 1.97 vs. 2.3 ± 0.82, P < 0.01) in the univariate analysis. Multivariate analysis revealed that SR> 3.0 was a significant predictor of thromboembolic events after coil embolization for unruptured BAAs (odds ratio: 12.15; 95% confidence interval: 2.95-49.98; P < 0.01). CONCLUSIONS: This study showed that SR is a predictor of thromboembolic events after coil embolization for unruptured BAAs. Therefore, if even in small BAAs, if the BAAs dome height is large compared to the diameter of the posterior cerebral artery (e.g., there is a large SR), preoperative evaluation of the use of antiplatelet therapy is important, particularly to prevent thromboembolic events.


Embolization, Therapeutic , Intracranial Aneurysm , Thromboembolism , Humans , Intracranial Aneurysm/diagnostic imaging , Intracranial Aneurysm/therapy , Intracranial Aneurysm/complications , Retrospective Studies , Embolization, Therapeutic/adverse effects , Embolization, Therapeutic/methods , Diffusion Magnetic Resonance Imaging , Blood Vessel Prosthesis/adverse effects , Thromboembolism/diagnostic imaging , Thromboembolism/epidemiology , Thromboembolism/etiology , Treatment Outcome
20.
Acta Neurochir (Wien) ; 165(6): 1575-1584, 2023 06.
Article En | MEDLINE | ID: mdl-37119319

BACKGROUND: The effect of posterior cranial fossa stroke on changes in cerebral volume is not known. We assessed cerebral volume changes in patients with acute posterior fossa stroke using CT scans, and looked for risk factors for cerebral atrophy. METHODS: Patients with cerebellar or brainstem hemorrhage/infarction admitted to the ICU, and who underwent at least two subsequent inpatient head CT scans during hospitalization were included (n = 60). The cerebral volume was estimated using an automatic segmentation method. Patients with cerebral volume reduction > 0% from the first to the last scan were defined as the "cerebral atrophy group (n = 47)," and those with ≤ 0% were defined as the "no cerebral atrophy group (n = 13)." RESULTS: The cerebral atrophy group showed a significant decrease in cerebral volume (first CT scan: 0.974 ± 0.109 L vs. last CT scan: 0.927 ± 0.104 L, P < 0.001). The mean percentage change in cerebral volume between CT scans in the cerebral atrophy group was -4.7%, equivalent to a cerebral volume of 46.8 cm3, over a median of 17 days. The proportions of cases with a history of hypertension, diabetes mellitus, and median time on mechanical ventilation were significantly higher in the cerebral atrophy group than in the no cerebral atrophy group. CONCLUSIONS: Many ICU patients with posterior cranial fossa stroke showed signs of cerebral atrophy. Those with rapidly progressive cerebral atrophy were more likely to have a history of hypertension or diabetes mellitus and required prolonged ventilation.


Brain Stem Infarctions , Stroke , Humans , Stroke/diagnostic imaging , Stroke/etiology , Cerebellum/pathology , Tomography, X-Ray Computed , Brain Stem Infarctions/pathology , Cranial Fossa, Posterior/diagnostic imaging , Cranial Fossa, Posterior/pathology , Atrophy
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