Human exposure to microplastics contained in food has become a significant concern owing to the increasing accumulation of microplastics in the environment. In this paper, we summarize the presence ...of microplastics in food and the analytical methods used for isolation and identification of microplastics. Although a large number of studies on seafood such as fish and shellfish exist, estimating the overall human exposure to microplastics via food consumption is difficult owing to the lack of studies on other food items. Analytical methods still need to be optimized for appropriate recovery of microplastics in various food matrices, rendering a quantitative comparison of different studies challenging. In addition, microplastics could be added or removed from ingredients during processing or cooking. Thus, research on processed food is crucial to estimate the contribution of food to overall human microplastic consumption and to mitigate this exposure in the future.
The unified bioaccessibility research group of Europe (BARGE) method (UBM) suggests using in vitro experimental conditions for simulating the release of chemicals from confined matrices, such as ...soils and sediments, in the human gastrointestinal tract. It contains comprehensive steps that simulate human digestion pathways and has good potential for application in the leaching of plastic additives from accidentally ingested plastic particles. However, its complexity could be a challenge for routine screening assessments of the migration of chemicals from consumer plastic products. In this study, the UBM was modified to assess the migration of plastic additives from consumer products with five model phthalate esters (i.e., dibutyl phthalate (DBP), benzyl butyl phthalate (BBP), bis(2-ethylhexyl) phthalate (DEHP), and di-
-octyl phthalate (DNOP)) from polyvinyl chloride (PVC). The migration of phthalate esters was observed in four digestive phases (saliva, gastric, duodenal, and bile). Three separate experiments were conducted with the addition of (1) inorganic constituents only, (2) inorganic and organic constituents, and (3) inorganic and organic constituents in combination with digestive enzymes. While using enzymes with the UBM solution, the migrated mass for leached compounds was comparatively low (0.226 ± 0.04 μg) in most digestion phases, likely due to a self-generated coating of enzymes on the plastic materials. However, higher mass migration (0.301 ± 0.05) was observed when phthalate esters were analyzed in the UBM solution, excluding the enzymes. A ring test among six independent laboratories confirmed the robustness of the modified method. Therefore, we propose a simplified version of the original UBM designed mainly for the migration of inorganic elements using only the inorganic and organic components of the solution throughout all phases of digestion.
Plasticizers are added to diverse consumer products including children's products. Owing to their potential for endocrine disruption, the use of phthalate plasticizers is restricted in many ...children's products. In this study, exposure to five phthalate esters (dibutylphthalate, di(2-ethylhexyl) phthalate (DEHP), diethyl phthalate, di-isobutyl phthalate, and diisononyl phthalate (DINP)) and an alternative (di-ethylhexyl adipate) was assessed by the use of children's products based on chemical analysis of 3345 products purchased during 2017 and 2019 in Korea. Plasticizers were found above the detection limits in 387 products, and DEHP and DINP were the two most predominantly detected plasticizers. Deterministic and probabilistic estimation of the margin of exposure at a screening level revealed that the use of children's products might be an important risk factor. However, it is also highly likely that the exposure could be overestimated, because the migration rate was estimated based solely on the content of plasticizers in children's products. Chemical migration is a key process determining the absorption of plasticizers from products; thus, further refinements in experimental determination or model estimation of the migration rate are required.
There is intense interest in developing curative interventions for HIV. How such a cure will be quantified and defined is not known. We applied a series of measurements of HIV persistence to the ...study of an HIV-infected adult who has exhibited evidence of cure after allogeneic hematopoietic stem cell transplant from a homozygous CCR5Δ32 donor. Samples from blood, spinal fluid, lymph node, and gut were analyzed in multiple laboratories using different approaches. No HIV DNA or RNA was detected in peripheral blood mononuclear cells (PBMC), spinal fluid, lymph node, or terminal ileum, and no replication-competent virus could be cultured from PBMCs. However, HIV RNA was detected in plasma (2 laboratories) and HIV DNA was detected in the rectum (1 laboratory) at levels considerably lower than those expected in ART-suppressed patients. It was not possible to obtain sequence data from plasma or gut, while an X4 sequence from PBMC did not match the pre-transplant sequence. HIV antibody levels were readily detectable but declined over time; T cell responses were largely absent. The occasional, low-level PCR signals raise the possibility that some HIV nucleic acid might persist, although they could also be false positives. Since HIV levels in well-treated individuals are near the limits of detection of current assays, more sensitive assays need to be developed and validated. The absence of recrudescent HIV replication and waning HIV-specific immune responses five years after withdrawal of treatment provide proof of a clinical cure.
Glioblastoma is a highly lethal neoplasm that frequently recurs locally after radiotherapy, and most of these recurrences originate from near the irradiated target field. In the present study, we ...identified the effects of radiation on glioma invasion and p53, TIMP-2, and MMP-2 expression through in vitro and in vivo experiments.
The U87MG (wt p53) and U251 (mt p53) human malignant glioma cell lines were prepared, and the U2OS (wt 53) and Saos2 (del p53) osteosarcoma cell lines were used as p53 positive and negative controls. The four cell lines and p53 knock-downed U87MG cells received radiation (2-6 Gy) and were analyzed for expression of p53 and TIMP-2 by Western blot, and MMP-2 activity was detected by zymography. In addition, the effects of irradiation on directional invasion of malignant glioma were evaluated by implanting nude mice with bioluminescent u87-Fluc in vivo followed by MMP-2, p53, and TIMP-2 immunohisto-chemistry and in situ zymography.
MMP-2 activity and p53 expression increased in proportional to the radiation dose in cell lines with wt p53, but not in the cell lines with del or mt p53. TIMP-2 expression did not increase in U87MG cells. MMP-2 activity decreased in p53 knock-downed U87MG cells but increased in the control group. Furthermore, radiation enhanced MMP-2 activity and increased tumor margin invasiveness in vivo. Tumor cells invaded by radiation overexpressed MMP-2 and p53 and revealed high gelatinolytic activity compared with those of non-radiated tumor cells.
Radiation-induced upregulation of p53 modulated MMP-2 activity, and the imbalance between MMP-2 and TIMP-2 may have an important role in glioblastoma invasion by degrading the extracellular matrix. Bioluminescent "U87-Fluc"was useful for observing tumor formation without sacrifice after implanting tumor cells in the mouse brain. These findings suggest that the radiotherapy involved field for malignant glioma needs to be reconsidered, and that future trials should investigate concurrent pharmacologic therapies that inhibit invasion associated with radiotherapy.
In-situ plasma-enhanced atomic layer deposition (PEALD) technique was employed for device passivation to realize a high-performance inversion-mode HfO 2 /In 0.53 Ga 0.47 As metal-oxide-semiconductor ...field-effect transistor (MOSFET). Excellent quality of gate dielectric is enabled by utilizing the PEALD-aluminum nitride as a pre-gate interfacial layer, followed by a post-gate remote-plasma gas treatment. In-situ PEALD treatment led to enhanced dc characteristics, such as drain current, peak transconductance, subthreshold swing, OFF leakage current, and effective electron mobility. X-ray photoelectron spectroscopy analysis indicates a reduction of In- and Ga-related signals. Furthermore, small drain current hysteresis and low-interface state density (D it ) value confirm a high interfacial quality for the high-k/III-V structure. Overall, the PEALD passivation for HfO 2 /In 0.53 Ga 0.47 As interface shows a remarkable improvement on the MOSFET performance.
Water extract of Raphanus sativus L. (RSL) seeds was traditionally used to treat digestive inflammatory complaints in Korean culture. RSL seeds exerted antioxidant, anti-inflammatory, and anti-septic ...functions, suggesting their pharmacological potential for the treatment of inflammatory pathologies associated with oxidative stress such as inflammatory bowel disease.
We evaluated the intestinal anti-inflammatory effects of RSL seed water extract (RWE) in experimental rat models of trinitrobenzenesulphonic acid (TNBS)- or dextran sodium sulfate (DSS)-induced colitis.
RWE was characterized by determining the content of sinapic acid as a reference material and then assayed in the DSS and TNBS models of rat colitis. Male Sprague–Dawley rats were divided into 10 groups (n=7/group): non-colitic control, DSS or TNBS control, DSS colitis groups treated with RWE (100mg/kg) or mesalazine (25mg/kg), and TNBS colitis groups treated with various doses (10, 40, 70, and 100mg/kg) of RWE or mesalazine (25mg/kg). RWE or mesalazine treatment started the same day of colitis induction and rats were sacrificed 24h after the last treatment followed by histological and biochemical analyses.
Oral administration with RWE suppressed intestinal inflammatory damages in both DSS- and TNBS-induced colitic rats. The treatment with 100mg/kg RWE recovered intestinal damages caused by TNBS or DSS to levels similar to that of mesalazine, decreasing the activity of myeloperoxidase activity and the secretion of tumor necrosis factor (TNF)-α and interleukin (IL)-1β. RWE treatment inhibited malondialdehyde production and glutathione reduction in colon of colitis rats. The administration of RWE at dose of 100mg/kg also suppressed the TNBS- or DSS-stimulated expression of TNF-α, IL-1β, monocyte chemotactic protein-1, inducible nitric oxide, and intercellular adhesion molecule-1. Furthermore, RWE inhibited p38 kinase and DNA–nuclear factor-κB binding activities, both of which were stimulated in the colitic rats.
The current findings show that RWE ameliorates intestinal oxidative and inflammatory damages in DSS and TNBS models of rat colitis, suggesting its beneficial use for the treatment of intestinal inflammatory disorders.
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Clonal evolution drives cancer progression and therapeutic resistance. Recent studies have revealed divergent longitudinal trajectories in gliomas, but early molecular features steering posttreatment ...cancer evolution remain unclear. Here, we collected sequencing and clinical data of initial-recurrent tumor pairs from 544 adult diffuse gliomas and performed multivariate analysis to identify early molecular predictors of tumor evolution in three diffuse glioma subtypes. We found that
deletion at initial diagnosis preceded tumor necrosis and microvascular proliferation that occur at later stages of IDH-mutant glioma. Ki67 expression at diagnosis was positively correlated with acquiring hypermutation at recurrence in the IDH-wild-type glioma. In all glioma subtypes,
gain or
target activation at diagnosis was associated with treatment-induced hypermutation at recurrence. To predict glioma evolution, we constructed CELLO2 (Cancer EvoLution for LOngitudinal data version 2), a machine learning model integrating features at diagnosis to forecast hypermutation and progression after treatment. CELLO2 successfully stratified patients into subgroups with distinct prognoses and identified a high-risk patient group featured by
gain with worse post-progression survival, from the low-grade IDH-mutant-noncodel subtype. We then performed chronic temozolomide-induction experiments in glioma cell lines and isogenic patient-derived gliomaspheres and demonstrated that MYC drives temozolomide resistance by promoting hypermutation. Mechanistically, we demonstrated that, by binding to open chromatin and transcriptionally active genomic regions, c-MYC increases the vulnerability of key mismatch repair genes to treatment-induced mutagenesis, thus triggering hypermutation. This study reveals early predictors of cancer evolution under therapy and provides a resource for precision oncology targeting cancer dynamics in diffuse gliomas.
Abstract Introduction Several clinical studies using tacrolimus revealed reasonable therapeutic mechanisms and efficacy in patients with myasthenia gravis (MG). However, long-period studies in a ...large number of patients with MG are limited; therefore, the aim of this study was to investigate the therapeutic efficacies and safety of tacrolimus in patients with MG during a 12-month follow-up period. Methods Tacrolimus was administered to 150 patients with MG who were recruited based on the inclusion criteria. Fifteen medical centers in Korea participated in this study. The efficacy of tacrolimus was assessed using MG composite scales (MGCS) and the prednisolone-sparing effect. And the adverse drug reactions (ADRs) of tacrolimus were monitored in each patient from the beginning of tacrolimus treatment to the end of the follow-up period. Results After starting tacrolimus, the 32 patients were affected by ADRs, and consequentially 134 patients of the enrolled patients were followed up for 12 months. They showed that the mean prednisolone dosage significantly decreased (6.1 ± 7.6 mg/day), compared to that in the baseline (11.3 ± 9.5 mg/day), and MGCS significantly improved after 12 months of tacrolimus treatment, compared to that at the baseline. Conclusions Our study showed that tacrolimus would be an effective immunosuppressant as an initial therapeutic agent in patients with MG; in addition, it showed tolerable safety profiles during the 12-month follow-up evaluation.
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