The human microbiome plays an essential role in the human immune system, food digestion, and protection from harmful bacteria by colonizing the human intestine. Recently, although the human ...microbiome affects colorectal cancer (CRC) treatment, the mode of action between the microbiome and CRC remains unclear. This study showed that propionate suppressed CRC growth by promoting the proteasomal degradation of euchromatic histone-lysine N-methyltransferase 2 (EHMT2) through HECT domain E3 ubiquitin protein ligase 2 (HECTD2) upregulation. In addition, EHMT2 downregulation reduced the H3K9me2 level on the promoter region of tumor necrosis factor α-induced protein 1 (TNFAIP1) as a novel direct target of EHMT2. Subsequently, TNFAIP1 upregulation induced the apoptosis of CRC cells. Furthermore, using Bacteroides thetaiotaomicron culture medium, we confirmed EHMT2 downregulation via upregulation of HECTD2 and TNFAIP1 upregulation. Finally, we observed the synergistic effect of propionate and an EHMT2 inhibitor (BIX01294) in 3D spheroid culture models. Thus, we suggest the anticancer effects of propionate and EHMT2 as therapeutic targets for colon cancer treatment and may provide the possibility for the synergistic effects of an EHMT2 inhibitor and microbiome in CRC treatment.
To determine optimal quarantine duration, we evaluated time from exposure to diagnosis for 107 close contacts of severe acute respiratory syndrome coronavirus 2 Omicron variant case-patients. Average ...time from exposure to diagnosis was 3.7 days; 70% of diagnoses were made on day 5 and 99.1% by day 10, suggesting 10-day quarantine.
In South Korea, a November 2021 outbreak caused by severe acute respiratory syndrome coronavirus 2 Omicron variant originated from 1 person with an imported case and spread to households, ...kindergartens, workplaces, restaurants, and hospitals, resulting in 11 clusters within 3 weeks. An epidemiologic curve indicated rapid community transmission of the Omicron variant.
Electrochemical CO
2
reduction (CO2RR) has received much attention for its ability to generate value-added chemicals from a molecule that would otherwise be a waste end-product. Numerous studies have ...emerged in the past decades, but the renewable and sustainable carbon-neutral CO
2
reduction process is yet to be industrialized. Here, we review the progress and bottlenecks of the electrochemical CO
2
reduction technologies over the past 15 years (2004-2018) to examine whether CO2RR process is to be applicable in a large-scale. Although the techno-economic analysis and pilot plants based on liquid-phase electrolysis have shown some positive results, current densities of the liquid-phase electrochemical CO
2
reduction are well below what techno-economic analyzes have projected due to its intrinsic limitations of solubility. On the other hand, the gas-phase electrolysis of CO
2
has shown superior performance parameters compared to the liquid-phase electrolysis, especially in the current densities, showing commercial viability although its techno-economic analysis is yet to be performed. Herein, we offer some perspectives and guidelines where future research in CO
2
electrolysis should aim. Based on the performance parameters obtained from the lab-scale gas-phase reactions, we believe that the current negative outlooks towards the industrial feasibility of the CO
2
electrolysis system could turn to positive views.
Human pluripotent stem cell (hPSC)-derived intestinal organoids (hIOs) form 3D structures organized into crypt and villus domains, making them an excellent in vitro model system for studying human ...intestinal development and disease. However, hPSC-derived hIOs still require in vivo maturation to fully recapitulate adult intestine, with the mechanism of maturation remaining elusive. Here, we show that the co-culture with human T lymphocytes induce the in vitro maturation of hIOs, and identify STAT3-activating interleukin-2 (IL-2) as the major factor inducing maturation. hIOs exposed to IL-2 closely mimic the adult intestinal epithelium and have comparable expression levels of mature intestinal markers, as well as increased intestine-specific functional activities. Even after in vivo engraftment, in vitro-matured hIOs retain their maturation status. The results of our study demonstrate that STAT3 signaling can induce the maturation of hIOs in vitro, thereby circumventing the need for animal models and in vivo maturation.
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•Pluripotent stem cell (PSC)-derived expandable human hepatocyte-like liver organoids were generated.•PSC-derived human hepatic organoids are capable of long-term expansion with ...competent liver functionality.•PSC-derived human hepatic organoids provide a robust hepatic model for toxicity prediction and drug screening.
The development of hepatic models capable of long-term expansion with competent liver functionality is technically challenging in a personalized setting. Stem cell-based organoid technologies can provide an alternative source of patient-derived primary hepatocytes. However, self-renewing and functionally competent human pluripotent stem cell (PSC)-derived hepatic organoids have not been developed.
We developed a novel method to efficiently and reproducibly generate functionally mature human hepatic organoids derived from PSCs, including human embryonic stem cells and induced PSCs. The maturity of the organoids was validated by a detailed transcriptome analysis and functional performance assays. The organoids were applied to screening platforms for the prediction of toxicity and the evaluation of drugs that target hepatic steatosis through real-time monitoring of cellular bioenergetics and high-content analyses.
Our organoids were morphologically indistinguishable from adult liver tissue-derived epithelial organoids and exhibited self-renewal. With further maturation, their molecular features approximated those of liver tissue, although these features were lacking in 2D differentiated hepatocytes. Our organoids preserved mature liver properties, including serum protein production, drug metabolism and detoxifying functions, active mitochondrial bioenergetics, and regenerative and inflammatory responses. The organoids exhibited significant toxic responses to clinically relevant concentrations of drugs that had been withdrawn from the market due to hepatotoxicity and recapitulated human disease phenotypes such as hepatic steatosis.
Our organoids exhibit self-renewal (expandable and further able to differentiate) while maintaining their mature hepatic characteristics over long-term culture. These organoids may provide a versatile and valuable platform for physiologically and pathologically relevant hepatic models in the context of personalized medicine.
A functionally mature, human cell-based liver model exhibiting human responses in toxicity prediction and drug evaluation is urgently needed for pre-clinical drug development. Here, we develop a novel human pluripotent stem cell-derived hepatocyte-like liver organoid that is critically advanced in terms of its generation method, functional performance, and application technologies. Our organoids can contribute to the better understanding of liver development and regeneration, and provide insights for metabolic studies and disease modeling, as well as toxicity assessments and drug screening for personalized medicine.
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Ulcerative colitis (UC) is an inflammatory bowel disease accompanied by abdominal pain, diarrhea, and rectal bleeding. The aim of this study was to investigate whether puerarin, one ...of the main components of the root of Pueraria lobata, exerts anti-inflammatory and anti-oxidative effects against UC. To examine the anti-inflammatory and anti-oxidative effects of puerarin against colitis, we used a mouse model of dextran sulfate sodium (DSS)-induced colitis. Administration of puerarin alleviated colon shortening, pathological damage to the colon, and myeloperoxidase (MPO) activity. Puerarin significantly inhibited inflammation through the down-regulation of nuclear factor-κB (NF-κB) and the secretion of pro-inflammatory mediators. Moreover, puerarin showed anti-oxidative effects through the regulation of the expression of the NF-E2 p45-related factor 2 (Nrf2) pathway and antioxidant enzymes. Puerarin inhibited intestinal epithelial barrier dysfunction by increasing the expression of tight junction proteins. These results suggest that puerarin has anti-inflammatory and anti-oxidative effects in the mouse model of colitis.
Electric energy forecasting domain attracts researchers due to its key role in saving energy resources, where mainstream existing models are based on Gradient Boosting Regression (GBR), Artificial ...Neural Networks (ANNs), Extreme Learning Machine (ELM) and Support Vector Machine (SVM). These models encounter high-level of non-linearity between input data and output predictions and limited adoptability in real-world scenarios. Meanwhile, energy forecasting domain demands more robustness, higher prediction accuracy and generalization ability for real-world implementation. In this paper, we achieve the mentioned tasks by developing a hybrid sequential learning-based energy forecasting model that employs Convolution Neural Network (CNN) and Gated Recurrent Units (GRU) into a unified framework for accurate energy consumption prediction. The proposed framework has two major phases: (1) data refinement and (2) training, where the data refinement phase applies preprocessing strategies over raw data. In the training phase, CNN features are extracted from input dataset and fed in to GRU, that is selected as optimal and observed to have enhanced sequence learning abilities after extensive experiments. The proposed model is an effective alternative to the previous hybrid models in terms of computational complexity as well prediction accuracy, due to the representative features' extraction potentials of CNNs and effectual gated structure of multi-layered GRU. The experimental evaluation over existing energy forecasting datasets reveal the better performance of our method in terms of preciseness and efficiency. The proposed method achieved the smallest error rate on Appliances Energy Prediction (AEP) and Individual Household Electric Power Consumption (IHEPC) datasets, when compared to other baseline models.
Cancer was thought to be caused solely by genetic mutations in oncogenes and tumor suppressor genes. In the last 35 years, however, epigenetic changes have been increasingly recognized as another ...primary driver of carcinogenesis and cancer progression. Epigenetic deregulation in cancer often includes mutations and/or aberrant expression of chromatin-modifying enzymes, their associated proteins, and even non-coding RNAs, which can alter chromatin structure and dynamics. This leads to changes in gene expression that ultimately contribute to the emergence and evolution of cancer cells. Studies of the deregulation of chromatin modifiers in cancer cells have reshaped the way we approach cancer and guided the development of novel anticancer therapeutics that target epigenetic factors. There remain, however, a number of unanswered questions in this field that are the focus of present research. Areas of particular interest include the actions of emerging classes of epigenetic regulators of carcinogenesis and the tumor microenvironment, as well as epigenetic tumor heterogeneity. In this review, we discuss past findings on epigenetic mechanisms of cancer, current trends in the field of cancer epigenetics, and the directions of future research that may lead to the identification of new prognostic markers for cancer and the development of more effective anticancer therapeutics.
The development of effective and safe repellents against arthropods is very important, because there are no effective vaccines against arthropod-borne viruses (arboviruses) and parasites. Arboviruses ...and parasites are transmitted to humans from arthropods, and mosquitoes are the most common arthropods associated with dengue, malaria, and yellow fever. Enormous efforts have been made to develop effective repellents against arthropods, and thus far synthetic repellents have been widely used. However, the use of synthetic repellents has raised several concerns in terms of environmental and human health risks and safety. Thus, plant essential oils (EOs) have been widely used as an alternative to synthetic repellents. In this review, we briefly introduce and summarize recent studies that have investigated EOs as insect repellents. Current technology and research trends to develop effective and safe repellents from plant EOs are also described in this review.
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