Exposure to toxic substances during postnatal period is one of the major factors causing retinal developmental defects. The developmental toxicity of trimethyltin chloride (TMT), a byproduct of an ...organotin compound widely used in agriculture and industrial fields, has been reported; however, the effect on the mammalian retina during postnatal development and the mechanism have not been elucidated to date. We exposed 0.75 and 1.5 mg/kg of TMT to neonatal ICR mice (1:1 ratio of male and female) up to postnatal day 14 and performed analysis of the retina: histopathology, apoptosis, electrophysiological function, glutamate concentration, gene expression, and fluorescence immunostaining. Exposure to TMT caused delayed eye opening, eye growth defect and thinning of retinal layer. In addition, apoptosis occurred in the retina along with b-wave and spiking activity changes in the micro-electroretinogram. These changes were accompanied by an increase in the concentration of glutamate, upregulation of astrocyte-related genes, and increased expression of glial excitatory amino acid transporter (EAAT) 1 and 2. Conversely, EAAT 3, 4, and 5, mainly located in the neurons, were decreased. Our results are the first to prove postnatal retinal developmental neurotoxicity of TMT at the mammalian model and analyze the molecular, functional as well as morphological aspects to elucidate possible mechanisms: glutamate toxicity with EAAT expression changes. These mechanisms may suggest not only a strategy to treat but also a clue to prevent postnatal retina developmental toxicity of toxic substances.
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•Postnatal exposure to TMT causes eye growth defect and thinning of the retina.•TMT induces apoptosis and impairs retinal function in the micro-electroretinogram.•TMT increases glutamate concentration and induces excitotoxicity in the retina.•TMT alters expression of excitatory amino acid transporters in the retina.•This is the first study to confirm the retinal developmental neurotoxicity of TMT.
Triclosan (TCS) is an organic compound with a wide range of antibiotic activity and has been widely used in items ranging from hygiene products to cosmetics; however, recent studies suggest that it ...has several adverse effects. In particular, TCS can be passed to both fetus and infants, and while some evidence suggests in vitro neurotoxicity, there are currently few studies concerning the mechanisms of TCS-induced developmental neurotoxicity. Therefore, this study aimed to clarify the effect of TCS on neural development using zebrafish models, by analyzing the morphological changes, the alterations observed in fluorescence using HuC-GFP and Olig2-dsRED transgenic zebrafish models, and neurodevelopmental gene expression. TCS exposure decreased the body length, head size, and eye size in a concentration-dependent manner in zebrafish embryos. It increased apoptosis in the central nervous system (CNS) and particularly affected the structure of the CNS, resulting in decreased synaptic density and shortened axon length. In addition, it significantly up-regulated the expression of genes related to axon extension and synapse formation such as α1-Tubulin and Gap43, while decreasing Gfap and Mbp related to axon guidance, myelination and maintenance. Collectively, these changes indicate that exposure to TCS during neurodevelopment, especially during axonogenesis, is toxic. This is the first study to demonstrate the toxicity of TCS during neurogenesis, and suggests a possible mechanism underlying the neurotoxic effects of TCS in developing vertebrates.
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•TCS changes craniofacial morphology and neural structures in zebrafish embryos.•TCS affects the expression of apoptosis and neurogenesis related genes.•TCS is toxic to neurodevelopmental stages, especially in axonogenesis.•This is the first study to confirm the developmental neurotoxicity of TCS.
This study first identifies potential mechanisms of developmental neurotoxicity that can occur when the organic compound triclosan is transmitted to developing vertebrate embryos.
White bulb colors of onion (
Allium cepa
L.) are determined by the
C
and
I
loci which control the so-called recessive and dominant white bulb colors, respectively. To identify the causal gene ...responsible for the
I
locus, a combined approach of bulked segregant analysis and RNA-Seq was used in the present study. A total of 68 contigs containing homozygous single nucleotide polymorphisms (SNPs) between red and dominant white bulked RNAs were identified. The position of
I
locus was found to be located at chromosome 3 by performing comparative analysis of these contigs and using a previously constructed linkage map. After verification of homozygous SNPs by sequencing of PCR products, 12 high resolution melting, one cleaved amplified polymorphic sequence, and one InDel markers were developed. A linkage map flanking the
I
locus was constructed using these markers. Two tightly linked markers (DW51596 and DW35019) flanking the
I
locus were identified by analyzing 1457 F
4
individuals. A total of 104 and 39 contigs showing more than tenfold increase of expression in red and dominant white bulks, respectively, were identified. Transcriptions of all structural genes encoding enzymes in flavonoid biosynthesis pathway were significantly reduced in the dominant white bulk. Transcription levels of most contigs showing more than tenfold reduced expression in dominant white were also significantly reduced in the recessive white bulbs controlled by the
C
locus. Genomic DNA sequences of 12 genes encoding transcription factors assumed to regulate flavonoid biosynthesis were analyzed. However, the causal gene for the
I
locus could not be identified.
The aim of this study is to investigate the change in flavonoid composition and antioxidative activity during fermentation of onion (Allium cepa L.) by Leuconostoc mesenteroides with different NaCl ...concentrations. In order to qualify and quantify the flavonoids during fermentation of onion, 7 flavonoids, quercetin 3,7‐O‐β‐d‐diglucopyranoside (Q3,7G), quercetin 3,4′‐O‐β‐d‐diglucopyranoside (Q3,4′G), quercetin 3‐O‐β‐d‐glucopyranoside (Q3G), quercetin 4′‐O‐β‐d‐glucopyranoside (Q4′G), isorhamnetin 3‐O‐β‐d‐glucopyranoside (IR3G), quercetin (Q), and isorhamnetin (IR), were isolated and identified from onion. During fermentation, the contents of flavonoid glucosides (Q3,7G, Q3,4′G, Q3G, Q4′G, and IR3G) gradually decreased, whereas the contents of flavonoid aglycones (Q, IR) gradually increased. Decline rates of the flavonoid glucosides increased with the addition of L. mesenteroides. Furthermore, the activity of β‐glucosidase, which is produced by L. mesenteroides, is dose‐dependently inhibited with different NaCl concentrations during fermentation. The presence of L. mesenteroides enhanced the antioxidative activity of onion as demonstrated using the 1,1‐diphenyl‐2‐picrylhydrazyl, 2,2′‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulfonic acid), and reducing power assays. The enhancement of antioxidative activity was considered because the content of flavonoid aglycones increased during fermentation. However, the addition of NaCl may decrease the antioxidative activity; we surmise that this phenomenon occurs because of the inhibition of β‐glucosidase by NaCl. Therefore, we conclude that the addition of NaCl may be useful for the regulation of antioxidative activity via the control of β‐glucosidase action, during the fermentation of flavonoid glucoside‐rich foods.
Practical Application
In this study, we have suggested that NaCl could act as a potential regulator of the antioxidative capacity of fermented foods such as kimchi and pickles. Therefore, the results may provide a new approach to control the quality of fermented foods.
This study investigated the effect of stress during the COVID-19 pandemic and the potential moderating effects of socioenvironmental factors on the physical conditions of Korean people with ...disabilities. Data from 405 participants on depression, instrumental activities of daily living and socioenvironmental factors were analyzed using frequency analysis, descriptive statistics, t-tests, one-way analysis of variance, Pearson's correlations and hierarchical regression analysis. Stress caused by COVID-19 was significantly correlated with depression, instrumental activities of daily living and social participation. Using socioenvironmental factors as moderators of the relationship between stress and depression, we found that increased depression was alleviated by social attitudes (β = 2.064; P < 0.01), family attitudes (β = 2.028; P < 0.05) and healthcare services and policies (β = -4.579; P < 0.001). Moreover, instrumental activities of daily living increased with decreased stress as moderated by social attitudes (β = 0.140; P < 0.05) and healthcare services and policies (β = -0.306; P < 0.001). Further, increased social participation alleviated stress as moderated by social attitudes (β = 0.106; P < 0.01), mobility and convenience facilities (β = 0.158; P < 0.01) and healthcare services and policies (β = -0.342; P < 0.001). The results indicate that even in public healthcare crises, it is important for people with disabilities to manage their health and participate in social activities. Their self-management and social participation can be promoted by strengthening community-centered rehabilitation and providing consumer-oriented social services.
Abstract Objective To evaluate the prognostic influence of adenocarcinoma (AC) and adenosquamous carcinoma (ASC) in patients with FIGO stage IB–IIA cervical cancer who received radical hysterectomy ...followed by adjuvant radiotherapy (RT) or concurrent chemoradiotherapy (CCRT). Methods We analyzed 1323 patients who satisfied the following criteria: histologically proven squamous cell carcinoma (SCC), AC, or ASC of the uterine cervix; FIGO stage IB–IIA disease; no history of neoadjuvant chemotherapy; and a history of radical hysterectomy with pelvic lymph node (PLN) dissection, followed by postoperative pelvic RT at a dose ≥ 45 Gy. The median age was 50 years. Median RT dose delivered to the whole pelvis was 50.4 Gy, and 219 (16.6%) patients received brachytherapy at a median dose of 24 Gy. Concurrent chemotherapy was delivered to 492 (37.2%) patients. Results Pathologic risk factors were not different according to pathologic subtype. The median follow-up duration was 75.7 months. Locoregional recurrence-free survival, relapse-free survival (RFS), and overall survival were significantly affected by histology, tumor size, PLN metastasis, parametrial invasion, lymphovascular invasion, and deep stromal invasion. The 5-year RFS rates were 83.7%, 66.5%, and 79.6% in patients with SCC, AC, and ASC histology, respectively ( P < 0.0001). By multivariate analysis, AC histology was the only significant prognostic factor affecting all survival outcomes. Conclusions AC histology was associated with poor survival outcomes in patients with FIGO stage IB–IIA cervical cancer who received adjuvant RT or CCRT. Prognosis of ASC histology was closer to that of SCC histology than that of AC histology.
The patterning of poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) hydrogels with excellent electrical property and spatial resolution is a challenge for bioelectronic ...applications. However, most PEDOT:PSS hydrogels are fabricated by conventional manufacturing processes such as photolithography, inkjet printing, and screen printing with complex fabrication steps or low spatial resolution. Moreover, the additives used for fabricating PEDOT:PSS hydrogels are mostly cytotoxic, thus requiring days of detoxification. Here, we developed a previously unexplored ultrafast and biocompatible digital patterning process for PEDOT:PSS hydrogel via phase separation induced by a laser. We enhanced the electrical properties and aqueous stability of PEDOT:PSS by selective laser scanning, which allowed the transformation of PEDOT:PSS into water-stable hydrogels. PEDOT:PSS hydrogels showed high electrical conductivity of 670 S/cm with 6-μm resolution in water. Furthermore, electrochemical properties were maintained even after 6 months in a physiological environment. We further demonstrated stable neural signal recording and stimulation with hydrogel electrodes fabricated by laser.
The right gastroepiploic artery (RGEA) has advantages for use as an arterial conduit in coronary artery bypass graft surgery but perioperative spasm often develops. This study assessed the spasm and ...occlusion rates of RGEA conduits and elucidated the mechanism of reopening of occluded RGEA conduits.
Patients who received an RGEA conduit in coronary artery bypass graft surgery were studied (n = 976; 700 composite, 276 in situ, 16 free grafts; 16 received both in situ and composite grafts). Early, 1-year, and 5-year angiographies were performed in 961 patients (98.5%), 815 patients (83.5%), and 618 patients (63.3%), respectively.
Graft spasm was demonstrated in early angiograms in 72 proximal graft trunks of 1,608 distal anastomoses (4.5%) constructed using an RGEA conduit. Early occlusion rates of composite, in situ, and free RGEA conduits were 1.1%, 2.5%, and 0%, respectively; 8.5%, 7.5%, and 21.4%, respectively, at 1 year; and 10.5%, 14.1%, and 37.5%, respectively, at 5 years. Nineteen of 23 patients who had RGEA conduit occlusions at early angiography (1 occluded anastomosis per patient) were reevaluated at 1 year, and 9 of them (47.4%) had become patent. Of 83 patients with occluded RGEA composite grafts (90 occluded RGEA conduit anastomoses) at 1-year angiography, 8 were reopened at 5 years (8.9%). Progression of native target coronary artery disease was observed in all 8 patients with reopened occluded RGEA conduits at 5 years but not in 9 patients with reopened RGEA conduits at 1 year.
Reopening of occluded RGEA conduits occurred early and midterm postoperatively. Reopening appeared related to recovery from graft spasm, and could occur as late as midterm if associated with progression of native coronary artery disease.
Pathogens can affect physiological and immunological reactions in immunocompromised animals and genetically engineered mice. Specifically, murine norovirus (MNV), Helicobacter, and intestinal ...protozoa are prevalent in rodent laboratory facilities worldwide. In this study, microbiological test results of the soiled bedding of sentinel mice showed the prevalence of MNV (50.9%, 28/55), Helicobacter hepaticus (29.1%, 16/55), Trichomonas spp. (14.5%, 8/55), and Entamoeba spp. (32.7%, 18/55). No single infections were detected as all cases were confirmed to have complex infections with two or four pathogens. In previous studies, the success rate of the cross-fostering method was not perfect; therefore, in this study, the entire mouse strain of the SPF rodent facility was rederived using embryo transfer. For up to three years, we confirmed that the results were negative with regular health surveillance tests. Embryo transfer was, thus, determined to be an effective method for the rederivation of specific pathogen free (SPF) barrier mouse facilities. This is the report for the effectiveness of embryo transfer as an example of successful microbiological clean-up of a mouse colony with multiple infections in an entire SPF mouse facility and embryo transfer may be useful for rederiving.
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