Basic performance assessment of reagents for measuring soluble FMS-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF) in Japanese women

Among the factors associated with angiogenesis, soluble FMS-like tyrosine kinase-1 (sFlt-1) is antiangiogenic and placental growth factor (PlGF) is proangiogenic. The sFlt-1/PlGF ratio is considered useful for the short-term prediction of preeclampsia (PE) in high-risk pregnancies and has been used clinically in Japan since July 2021. Regarding the clinical use of the sFlt-1/PlGF ratio in Japan, there have been no published reports demonstrating that sFlt-1 and PlGF assay reagents have the same basic performance in Japanese and European women. To our knowledge, we conducted the first basic performance assessment of the sFlt-1 and PlGF assay reagents using sera from Japanese women. We obtained satisfactory results for repeatability, intermediate precision, linearity, effects of interferents, and the LoQ. The sFlt-1 and PlGF assay reagents performed well, and we believe that they are entirely adequate for use in routine clinical assays of Japanese patients, similar to those in European patients

A 92-year-old man with retropharyngeal hematoma caused by an injury of the anterior longitudinal ligament

AbstractTraumatic retropharyngeal hematoma is a rare condition and may be lethal in some cases. In patients with this condition, the absence of a vertebral fracture or a major vascular injury is extremely rare. We present the case of a 92-year-old man who hit his forehead by slipping on the floor in his house. He had no symptoms at the time; however, he experienced throat pain and dyspnea at 6 hours after the injury. On arrival, he complained of severe dyspnea; therefore, an emergency endotracheal intubation was performed. A lateral neck roentgenogram after intubation showed dilatation of the retropharyngeal and retrotracheal space and no evidence of a cervical vertebral fracture. Cervical computed tomography (CT) with contrast medium revealed a massive hematoma extending from the retropharyngeal to the superior mediastinal space but no evidence of contrast medium extravasation or a vertebral fracture. However, sagittal magnetic resonance imaging (MRI) revealed an anterior longitudinal ligament (C4-5 levels) injury. We determined that the cause of the hematoma was an anterior longitudinal ligament injury and a minor vascular injury around the injured ligament. Therefore, we recommend that patients with retropharyngeal hematoma undergo sagittal cervical MRI when roentgenography and CT reveal no evidence of injury

Juvenile hormone synthesis and signaling disruption triggering male offspring induction and population decline in cladocerans (water flea): Review and adverse outcome pathway development

Juvenile hormone (JH) are a family of multifunctional hormones regulating larval development, molting, metamorphosis, reproduction, and phenotypic plasticity in arthropods. Based on its importance in arthropod life histories, many insect growth regulators (IGRs) mimicking JH have been designed to control harmful insects in agriculture and aquaculture. These JH analogs (JHAs) may also pose hazards to nontarget species by causing unexpected endocrine-disrupting (ED) effects such as molting and metamorphosis defects, larval lethality, and disruption of the sexual identity. This critical review summarizes the current knowledge of the JH-mediated effects in the freshwater cladoceran crustaceans such as Daphnia species on JHA-triggered endocrine disruptive outputs to establish a systematic understanding of JHA effects. Based on the current knowledge, adverse outcome pathways (AOPs) addressing the JHA-mediated ED effects in cladoceran leading to male offspring production and subsequent population decline were developed. The weight of evidence (WoE) of AOPs was assessed according to established guidelines. The review and AOP development aim to present the current scientific understanding of the JH pathway and provide a robust reference for the development of tiered testing strategies and new risk assessment approaches for JHAs in future ecotoxicological research and regulatory processes.publishedVersionacceptedVersio

Periostin as a novel biomarker for postoperative recurrence of chronic rhinosinitis with nasal polyps

We previously reported that chronic rhinosinusitis with nasal polyps (CRSwNP) was subdivided into four chronic rhinosinusitis (CRS) subtypes using the JESREC scoring system. We sought to identify the gene expression profile and biomarkers related with CRSwNP by RNA-sequence. RNA-sequencing was performed to identify differentially expressed genes between nasal polyps (NPs) and inferior turbinate mucosa from 6 patients with CRSwNP, and subsequently, quantitative real-time PCR was performed to verify the results. ELISA was performed to identify possible biomarkers for postoperative recurrence. In the RNA-sequencing results, periostin (POSTN) expression was the highest in NP. We focused on POSTN and investigated the protein level of POSTN by immunohistochemistry and ELISA. POSTN was diffusely expressed in moderate and severe eosinophilic CRS using immunohistochemistry, and its staining pattern was associated with the severity of the phenotype of the CRSwNP (P < 0.05). There was a significant difference between the POSTN high/low groups for postoperative recurrence when the cutoff point was set at 115.5 ng/ml (P = 0.0072). Our data suggests that the protein expression level of POSTN was associated with the severity of CRSwNP, and serum POSTN can be a novel biomarker for postoperative recurrence of CRSwNP

IL-6 receptor antibody treatment improves muscle weakness in experimental autoimmune myasthenia gravis mouse model

Myasthenia gravis (MG) is a chronic autoimmune disease characterized by muscle weakness and fatigue. It is caused by pathological autoantibodies against components expressed at neuromuscular junctions, such as acetylcholine receptor (AChR). Interleukin-6 (IL-6) has been suggested to play a role in the pathogenesis of MG, and IL-6 receptor (IL-6R) antibody treatment may provide a novel therapeutic option. In this study, we investigated the effects of IL-6R antibody treatment in an experimental autoimmune MG (EAMG) mouse model. We demonstrated that IL-6R antibody treatment improved muscle weakness, reduced IgG deposition at neuromuscular junctions, and the levels of AChR autoantibodies in serum. In addition, follicular helper T cells and Th17, plasma cells in lymph nodes were lower in IL-6R antibody treated mice. Our findings suggest that IL-6R blockade may be a novel and effective therapeutic strategy for the treatment of MG

532 nm low-power laser irradiation recovers γ-secretase inhibitor-mediated cell growth suppression and promotes cell proliferation via Akt signaling.

The γ-secretase inhibitor (GSI) has been shown to inhibit expression of amyloid beta (Aβ), but GSI also has a side effect of reducing cell survival. Since low-power laser irradiation (LLI) has been known to promote cell survival, we examined whether 532 nm LLI can rescue the GSI side effect or not.The human-derived glioblastoma cells (A-172) were cultured in 35 mm culture dishes or 96-well plate. The center of dish or selected wells was irradiated with 532 nm laser (Nd:YVO4, CW, 60 mW) for 20, 40 and 60 min, respectively. The irradiated cells were photographed at immediately after, 24 and 48 h later and counted. GSI was supplemented in medium 3 h before LLI. The MTT assay was also used to estimate viable cells at 48 h after irradiation. The expression of phosphorylated Akt (p-Akt) or phosphorylated PTEN (p-PTEN) was examined by immunofluorescent staining and measured by fluorescence intensity using the software (BZ-9000, KEYENCE, Japan).GSI application depressed cell proliferation as well as cell survival compared to control. GSI down-regulated Aβ but up-regulated p-PTEN and suppressed p-Akt. Application of 532 nm LLI in the presence of GSI significantly recovered the GSI-mediated effects, i.e., LLI could decrease elevated p-PTEN, while increased p-Akt expression with keeping Aβ suppression. The LLI effects had a dose-dependency.We confirmed that GSI potently suppressed intracellular Aβ and decreased cell survival. We conclude that a combination of GSI application and 532 nm LLI can increase cell proliferation via Akt activation while keeping PTEN and Aβ suppressed

Effects of LLI, DAPT and combined application of both on cell proliferation.

<p>Proliferation ratios for each group at 24 h and 48 h after LLI for control (white bars), 60 min LLI (light grey bars), DAPT (grey bars) or the combination of LLI and DAPT (dark grey bars) are shown. Asterisks: one-way ANOVA, * p<0.05, ** p<0.01.</p

Immunofluorescent staining of Akt and PTEN.

<p>A: The LLI effects on immunofluorescence staining of p-PTEN and p-Akt in cultures cells (bottom). Corresponding phase contrast micrographs are shown on top of each fluorescent image. It should be noted that tumor cells normally proliferate in high proportions and p-Akt is often highly expressed in cancer cells of different natures, whereas our result of control group shows low level of p-Akt expression due to haze reduction. Cal.: 100 µm. B: Average fluorescence intensity for p-PTEN or p-Akt normalized to the control value. Asterisks: one-way ANOVA, * p<0.05, ** p<0.01.</p

Effects of LLI on the number of A-172 cells.

<p>A: Sample images of A-172 cells under light microscope. The number of cells increased 48 h post-LLI (right column) after 20, 40, 60 min LLI compared to pre-LLI (left column). Cal.: 100 µm. B: Proliferation ratio (the ratio of cell number at 24 or 48 hours following LLI and cell number before LLI) was normalized to control (no LLI) (n = 12 for each group). C: A summary of colorimetric analysis by MTT staining performed at 48 h after LLI (each group: n = 16). The optical density of each group was normalized to the value of control group (no LLI) at 48 h after initial condition. Asterisks: one-way ANOVA, * p<0.05, ** p<0.01.</p