Summary
In a prospective, explorative study, the donor‐source difference of haploidentical family (HF), matched sibling (MS), and unrelated donors (UD) was evaluated for the outcome of haematopoietic ...cell transplantations (HCT) in 101 patients with acute myeloid leukaemia (AML) in complete remission (CR). To eliminate compounding effects, a uniform conditioning regimen containing antithymocyte globulin (ATG) was used. After transplantation, there was a significantly higher cumulative incidence of acute graft‐versus‐host disease (GVHD) in HF‐HCT patients (49%, 7%, and 16% for HF‐, MS‐ and UD‐HCT respectively; p < 0.001). A quarter of acute GVHD cases observed in HF‐HCT patients occurred within three days of engraftment and were characterized by diffuse skin rash, fever, weight gain, and hypoalbuminaemia. This peri‐engraftment acute GVHD was not observed in MS‐HCT or UD‐HCT patients. Additionally, a significantly higher proportion of HF‐HCT patients achieved complete donor chimaerism in the peripheral mononuclear cells at one month (88%, 46%, and 69% for HF‐, MS‐ and UD‐HCT respectively; p = 0.001). There was no significant difference in engraftment, chronic GVHD, leukaemia recurrence, non‐relapse mortality, and patient survival. In patients with AML in CR who received HCT using ATG‐containing conditioning, stronger donor–patient alloreactivity was observed in HF‐HCT, in terms of increased acute GVHD and higher likelihood of complete donor chimaerism.
Single-electron oxidation and α-deprotonation of tertiary anilines using Fe(phen)3(PF6)3 afford α-aminoalkyl radicals, which can be coupled with electrophilic partners to afford various ...tetrahydroquinolines. Mechanistically, the Fe(phen) n 2+/3+ catalytic cycle is maintained by O2 or a TBHP oxidant, and the presence of the oxygen bound iron complex, Fe(III)–OO(H), was elucidated by electron paramagnetic resonance and electrospray ionization mass spectrometry. This redox-selective nonheme iron catalyst behaves similarly to bioinspired heme iron catalysts.
a rapid and simple liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the determination of cannabidiol (CBD) and Δ
9
-tetrahydrocannabinol (THC) using a ...QuEChERS (Quick, Easy, Cheap, Effective, Rugged, and Safe) clean-up for a variety of foods and dietary supplements (DS). QuEChERS is widely used in extraction or clean-up procedures to eliminate interference of matrices such as sugars, organic acids, lipids, and fatty acids. The samples were categorised into three types, and various pretreatment methods were compared for each type. In all types, the QuEChERS was superior and selected as the final pretreatment method. The optimised method was validated for specificity, limit of detection (LOD), limit of quantification (LOQ), linearity, recovery, precision and accuracy. All of the validation results met the requirements of the international guidelines for all types of samples. The validated method was applied to 30 commercial food samples, CBD was detected in 17 samples, with 2 of them detected below the LOQ level and the rest detected in a range of 70 μg/kg to 31305 mg/kg (3.1%, w/w). Meanwhile, THC was detected in 14 samples; 2 of them were detected below the LOQ level and the rest detected in a 0.08-98.62 μg/g range. These results indicated that the validated method can be successfully applied for the determination of cannabinoids in a variety of samples. Furthermore, it will be useful for controlling the illegal distribution of cannabinoids.
The core functions of stem cells (SCs) are critically regulated by their cellular redox status. Glutathione is the most abundant non-protein thiol functioning as an antioxidant and a redox regulator. ...However, an investigation into the relationship between glutathione-mediated redox capacity and SC activities is hindered by lack of probe. Here, we demonstrate that cyanoacrylamide-based coumarin derivatives are ratiometric probes suitable for the real-time monitoring of glutathione levels in living SCs. These probes revealed that glutathione levels are heterogeneous among subcellular organelles and among individual cells and show dynamic changes and heterogeneity in repopulating SCs depending on oxidative stress or culture conditions. Importantly, a subpopulation of SCs with high glutathione levels exhibited increased stemness and migration activities in vitro and showed improved therapeutic efficiency in treating asthma. Our results indicate that high glutathione levels are required for maintaining SC functions, and monitoring glutathione dynamics and heterogeneity can advance our understanding of the cellular responses to oxidative stress.
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•FreSHtracer is a reversible probe for a fast and ratiometric reaction with GSH•FreSHtracer and its derivatives enable real-time monitoring of intracellular GSH•FreSHtracer reports dynamic changes and heterogeneity of GSH level in stem cells•High GSH levels are required for maintaining functional potency of stem cells
By developing and characterizing new fluorescent probes enabling fast, reversible, and ratiometric reaction with glutathione, Jeong et al. reveal considerable dynamics and heterogeneity in glutathione levels in living stem cells in response to environmental stress and also show that high glutathione levels are required for maintaining stemness of murine embryonic stem cells or therapeutic potency of mesenchymal stem cells.
With an increase in the detection of structural and functional analogues of phosphodiesterase type 5 inhibitors (PDE-5i) in dietary supplements (DS) and foods, public health is threatened. Some ...products advertise natural ingredients despite containing PDE-5i that can cause serious adverse effects on human health. To avoid detection during routine screening, novel PDE-5i have been synthesised and added to DS and foods. The purpose of this study was to detect, identify, and quantify 94 PDE-5i and related compounds in DS and foods. Furthermore, the study investigated the detection cases and compared them by sample type, formulation, and compounds. The HPLC and LC-MS/MS methods were validated for limit of detection (LOD), limit of quantification (LOQ), linearity, and recovery in solid and liquid type samples. Both HPLC and LC-MS/MS showed satisfactory results, which were in conformance with the ICH guidelines. A total of 404 samples, including DS (99), and foods (305) were purchased from online and offline markets. Samples divided into 5 types of formulation were analysed; tablet, capsule, pilula (herbal medicine pill), powder and liquid type. Of these 130 samples (47 of 99 DS, and 83 of 305 foods) contained one or more PDE-5i or related compounds. Among the five types of formulation, the tablet type showed the highest detection rate (61.1%) in DS, whereas the capsule type showed the highest detection rate (53.8%) in food samples. This study will be helpful for monitoring illegal ED-related products, providing information to consumers, and ultimately contributing to protecting public health.
Inflammatory pseudotumor (IPT)‐like follicular dendritic cell (FDC) sarcoma is a rare neoplasm typically occurring in the spleen or liver. We present six cases of EBV+ IPT‐like FDC sarcoma of the ...spleen among Koreans along with their clinicopathologic features and IHC results. Most patients presented with an asymptomatic, incidentally detected single splenic mass and were successfully managed by splenectomy alone. Concomitant disease was found in one case, showing EBV+ gastric carcinoma with lymphoid‐rich stroma. Histologic features showed fibro‐inflammatory lesions that were often accompanied by necrosis and epithelioid histiocytic collection, which are barely distinguishable from IPT. Tumor cells did not frequently express conventional FDC markers, including CD21 (3/6 positive cases), clusterin (4/6), and D2‐40 (2/6), but showed uniform positivity for smooth muscle actin (SMA). Noticeably, significant numbers of IgG4+ plasma cells were found within all six tumors. We suggest that the diagnosis of IPT‐like FDC sarcoma should be made by the application of a panel of FDC markers, and CD21 negativity or SMA positivity cannot be the criterion for exclusion of IPT‐like FDC sarcoma. Relationship of IPT‐like FDC sarcoma of the spleen and IgG4‐related sclerosing disease should be investigated in further studies.
A number of mobile health apps related to coronavirus infectious disease 2019 (COVID-19) have been developed, but research into app content analytics for effective surveillance and management is ...still in its preliminary stages. The present study aimed to identify the purpose and functions of the currently available COVID-19 apps using content analysis. The secondary aim was to propose directions for the future development of apps that aid infectious disease surveillance and control with a focus on enhancing the app content and quality. Prior to conducting an app search in the App Store and the Google Play Store, we reviewed previous studies on COVID-19 apps found in Google Scholar and PubMed to examine the main purposes of the apps. Using the five selected keywords based on the review, we searched the two app stores to retrieve eligible COVID-19 apps including those already addressed in the reviewed literature. We conducted descriptive and content analyses of the selected apps. We classified the purpose types of the COVID-19 apps into the following five categories: Information provision, tracking, monitoring, mental health management, and engagement. We identified 890 apps from the review articles and the app stores: 47 apps met the selection criteria and were included in the content analysis. Among the selected apps, iOS apps outnumbered Android apps, 27 apps were government-developed, and most of the apps were created in the United States. The most common function for the iOS apps (63.6%) and Android apps (62.5%) was to provide COVID-19-related knowledge. The most common function among the tracking apps was to notify users of contact with infected people by the iOS apps (40.9%) and Android apps (37.5%). About 29.5% of the iOS apps and 25.0% of the Android apps were used to record symptoms and self-diagnose. Significantly fewer apps targeted mental health management and engagement. Six iOS apps (6/44, 13.6%) and four Android apps (4/24, 16.7%) provided behavioral guidelines about the pandemic. Two iOS apps (2/44, 4.5%) and two Android apps (2/24, 8.3%) featured communication functions. The present content analysis revealed that most of the apps provided unilateral information and contact tracing or location tracking. Several apps malfunctioned. Future research and development of COVID-19 apps or apps for other emerging infectious diseases should address the quality and functional improvements, which should begin with continuous monitoring and actions to mitigate any technical errors.
Thyroid cancer is one of the most commonly detected cancers worldwide, and papillary thyroidal carcinoma (PTC) accounts for the majority of thyroid cancers. In contrast to the indolent nature of PTC, ...anaplastic thyroid carcinoma (ATC) shows an extremely poor prognosis and has not responded to any therapeutic modalities. Many researchers postulate that the dedifferentiation of thyroid follicular cells into primitive cells might be related to the pathogenesis of ATC because several cases of ATC have revealed pre-existing PTC lesions. Additionally, the cancer stem cell (CSC) theory has been widely accepted in the pathogenesis of ATC.
To explore the expression of various CSC markers in thyroid carcinoma tissues and analyse their clinical significance.
133 patients with PTC and 25 patients with ATC were enrolled. Immunohistochemistry for aldehyde dehydrogenase 1 (ALDH1), CD133, CXCR4, ATP-binding cassette (ABC)G2, multidrug resistance associated protein-1 (MRP1), lung resistance protein-1 (LRP), P-glycoprotein 1 (P-Gp1), SOX2, SOX9 and Oct4 was performed using tissue microarray.
CSC marker expression was significantly high in ATC, particularly chemoresistance markers such as ABCG2, MRP1, LRP and CXCR4. In PTC, ABCG2 was highly positive in more advanced pathological stages and was associated with lymph node involvement, with borderline significance. In ATC, high expression of CXCR4 correlated with distant metastasis, and LRP showed a tendency to correlate with lymph node metastasis. High expression of CSC markers was related to shorter overall survival in patients with ATC.
These results provide strong evidence that CSCs are related to the pathogenesis of ATC and can explain the frequent treatment failure and aggressiveness of ATC.
In this study, we describe the 3D chromosome regulatory landscape of human naive and primed embryonic stem cells. To devise this map, we identified transcriptional enhancers and insulators in these ...cells and placed them within the context of cohesin-associated CTCF-CTCF loops using cohesin ChIA-PET data. The CTCF-CTCF loops we identified form a chromosomal framework of insulated neighborhoods, which in turn form topologically associating domains (TADs) that are largely preserved during the transition between the naive and primed states. Regulatory changes in enhancer-promoter interactions occur within insulated neighborhoods during cell state transition. The CTCF anchor regions we identified are conserved across species, influence gene expression, and are a frequent site of mutations in cancer cells, underscoring their functional importance in cellular regulation. These 3D regulatory maps of human pluripotent cells therefore provide a foundation for future interrogation of the relationships between chromosome structure and gene control in development and disease.
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•ChIA-PET analysis maps enhancers and insulators into looped domains•Cohesin-associated loops organize topologically associating domains (TADs)•Regulatory changes during cell state transitions take place within TADs•The conserved anchors of CTCF-CTCF loops are frequently mutated in cancer
Ji et al. map the chromosome organizational structures that underlie gene regulation in human naive and primed pluripotent cells. Their framework of cohesin-associated CTCF loops, and the cohesin-associated enhancer-promoter loops within them, provides a reference map for future interrogation of regulatory interactions.
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