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Both lipid accumulation and inflammatory response in lesion macrophages fuel the progression of atherosclerosis, leading to high mortality of cardiovascular disease. A therapeutic strategy concurrently targeting these two risk factors is promising, but still scarce. Oridonin, the bioactive medicinal compound, is known to protect against inflammatory response and lipid dysfunction. However, its effect on atherosclerosis and the underlying molecular mechanism remain elusive. Here, we showed that oridonin attenuated atherosclerosis in hyperlipidemic ApoE knockout mice. Meanwhile, we confirmed the protective effect of oridonin on the oxidized low‐density lipoprotein (oxLDL)‐induced foam macrophage formation, resulting from increased cholesterol efflux, as well as reduced inflammatory response. Mechanistically, the network pharmacology prediction and further experiments revealed that oridonin dramatically facilitated the expression of peroxisome proliferator‐activated receptor gamma (PPARγ), thereby regulating liver X receptor‐alpha (LXRα)‐induced ATP‐binding cassette transporter A1 (ABCA1) expression and nuclear factor NF‐kappa‐B (NF‐κB) translocation. Antagonist of PPARγ reversed the cholesterol accumulation and inflammatory response mediated by oridonin. Besides, RNA sequencing analysis revealed that fatty acid binding protein 4 (FABP4) was altered responding to lipid modulation effect of oridonin. Overexpression of FABP4 inhibited PPARγ activation and blunted the benefit effect of oridonin on foam macrophages. Taken together, oridonin might have potential to protect against atherosclerosis by modulating the formation and inflammatory response in foam macrophages through FABP4/PPARγ signalling. [ABSTRACT FROM AUTHOR]

Macrophage‐derived foam cell formation is critical for the initiation and development of atherosclerosis, which contributes to atherosclerotic cardiovascular disease (ASCVD). Glutathione peroxidase 4 (GPX4), a crucial ferroptosis regulator, protects cells from excessive oxidative stress by neutralizing lipid peroxidation. However, the role of macrophage GPX4 in foam cell formation remains unknown. We reported that oxidized low‐density lipoprotein (oxLDL) upregulated GPX4 expression in macrophages. Using the Cre‐loxP system, we generated myeloid cell‐specific Gpx4 knockout (Gpx4myel‐KO) mice. Bone marrow‐derived macrophages (BMDMs) were isolated from WT and Gpx4myel‐KO mice and incubated with modified low‐density lipoprotein (LDL). We found that Gpx4 deficiency promoted foam cell formation and increased the internalization of modified LDL. Mechanistic studies unveiled that Gpx4 knockout upregulated scavenger receptor type A and LOX‐1 expression and downregulated ABCA1 and ABCG1 expression. Collectively, our study lends a novel insight into the role of GPX4 in suppressing macrophage‐derived foam cell formation and suggests GPX4 as a promising therapeutic target to interfere with atherosclerosis‐related diseases. [ABSTRACT FROM AUTHOR]

Simple Summary: The characteristics of high-pore-volume (high-PV) waterflooding and the mechanisms of enhanced oil recovery (EOR) are unclear. an experiment was conducted using nuclear magnetic resonance (NMR) technology-assisted waterflooding to monitor oil migration and pore structure changes during the displacement process. We quantified the ultimate oil displacement efficiency waterflooding and microscopic oil recovery at the pore scale. Additionally, the variations in petrophysical properties seen during this process were analyzed. The experiment revealed that the high-PV displacement process had a high EOR effect, even in the ultrahigh water cut stage. During this period, oil production came mainly from the mesopores. Furthermore, flooding changed the rock structure, increasing the pore volume. However, these changes were inconsistent at both the pore scale and spatial scale. At the pore scale, the volume of macropores decreased, while that of the micropores and mesopores increased. At the spatial scale, the porosity and the average pore size at the front end increased, while those at the back end decreased due to particle migration during flooding. Our findings suggested that pore structure variations at the front ends of experimental cores were representative of those in reservoirs, indicating that high-PV waterflooding could increase the permeabilities of reservoirs. A single paragraph of about 200 words maximum. For research articles, abstracts should give a pertinent overview of the work. We strongly encourage authors to use the following style of structured abstracts, but without headings: (1) Background: Place the question addressed in a broad context and highlight the purpose of the study; (2) Methods: briefly describe the main methods or treatments applied; (3) Results: summarize the article's main findings; (4) Conclusions: indicate the main conclusions or interpretations. The abstract should be an objective representation of the article and it must not contain results that are not presented and substantiated in the main text and should not exaggerate the main conclusions. [ABSTRACT FROM AUTHOR]

Oil pollution in soil-groundwater systems is difficult to remove, and a large amount of residual oil is trapped in the low permeable layer of the heterogeneous aquifer. Aromatic hydrocarbons in oil have high toxicity and low solubility in water, which are harmful to the ecological environment. Chemotactic degrading bacteria can perceive the concentration gradient of non-aqueous phase liquid (NAPL) pollutants in the groundwater environment, and enrich and proliferate around the pollutants, thus achieving a more efficient and thorough remediation effect. However, the existing theoretical models are relatively simple. The physical fields of oil–water two-phase flow and oil-phase solute convection and diffusion in water are not coupled, which further restricts the accuracy of studies on bacterial chemotaxis to NAPL. In this study, geometric models based on the actual microfluidic experimental study were constructed. Based on the phase field model, diffusion convection equation and chemotaxis velocity equation, the effects of heterogeneity of porous media, wall wettability and groundwater flow rate on the residual oil and the concentration distribution of chemotaxis bacteria were studied. Under all of the simulation conditions, the residual oil in the high permeable area was significantly lower than that in the low permeable area, and the wall hydrophilicity enhanced the water flooding effect. Chemotactic bacteria could react to the concentration gradient of pollutants dissolved into water in the oil phase, and enrich near the oil–water interface with high concentration of NAPL, and the density of chemotactic bacteria at the oil–water interface can be up to 1.8–2 times higher than that in the water phase at flow rates from 1.13 to 6.78 m/d. [ABSTRACT FROM AUTHOR]

Skeletal muscle plays a pivotal role in the maintenance of physical and metabolic health. Skeletal muscle atrophy usually results in physical disability, inferior quality of life and higher health care costs. The higher incidence of muscle atrophy in obese and ageing groups is due to increased levels of inflammatory factors during obesity and ageing. Dihydromyricetin, as a bioactive polyphenol, has been used for anti‐inflammatory, anti‐tumour and improving insulin sensitivity. However, there are no published reports demonstrated the dihydromyricetin effect on inflammation‐induced skeletal muscle atrophy. In this study, we first confirmed the role of dihydromyricetin in inflammation‐induced skeletal muscle atrophy in vivo and in vitro. Then, we demonstrated that dihydromyricetin resisted inflammation‐induced skeletal muscle atrophy by activating Ca2+‐CaMKK‐AMPK through signal pathway blockers, Ca2+ probes and immunofluorescence. Finally, we clarified that dihydromyricetin activated Ca2+‐CaMKK‐AMPK signalling pathway through interaction with the ryanodine receptor, its target protein, by drug affinity responsive target stability (DARTS). Our results not only demonstrated that dihydromyricetin resisted inflammation‐induced muscle atrophy via the ryanodine receptor‐CaMKK‐AMPK signal pathway but also discovered that the target protein of dihydromyricetin is the ryanodine receptor. Our results provided experimental data for the development of dihydromyricetin as a functional food and new therapeutic strategies for treating or preventing skeletal muscle atrophy. [ABSTRACT FROM AUTHOR]

Skeletal muscle, a critical component of the mammalian body, is essential for normal body movement. miRNAs are well documented in gene post-transcription regulation in many biological processes, including muscle development and maintenance. miR-92b-3p, which is often associated with tumorigenesis, has never been explored in myoblast development. Here, we used murine-derived C2C12 myoblasts to explore the potential functions of miR-92b-3p in skeletal muscle development. Our results demonstrated that miR-92b-3p mimics inhibited C2C12 cell proliferation and migration, whereas miR-92b-3p inhibitor promoted C2C12 cell proliferation and migration. C2C12 cell differentiation was not affected by miR-92b-3p mimics, according to immunofluorescence and qPCR results. Serum- and glucocorticoid-induced kinase 3 (SGK3) was predicted and validated as a target of miR-92b-3p. Overexpression of SGK3 promoted C2C12 cell proliferation. SGK3 and miR-92b-3p formed a regulatory pathway to modulate C2C12 cell proliferation. In conclusion, miR-92b-3p inhibited C2C12 cell proliferation by targeting SGK3 and impeded C2C12 cell migration. [ABSTRACT FROM AUTHOR]

Chinese indigenous pigs exhibit considerable phenotypic diversity, but their population structure and the genetic basis of agriculturally important traits need further exploration. Here, we sequenced the whole genomes of 24 individual pigs representing 22 breeds distributed throughout China. For comparison with European and commercial breeds (one pig per breed), we included seven published pig genomes with our new genomes for analyses. Our results showed that breeds grouped together based on morphological classifications are not necessarily more genetically similar to each other than to breeds from other groups. We found that genetic material from European pigs likely introgressed into five Chinese breeds. We have identified two new subpopulations of domestic pigs that encompass morphology-based criteria in China. The Southern Chinese subpopulation comprises the classical South Chinese Type and part of the Central China Type. In contrast, the Northern Chinese subpopulation comprises the North China Type, the Lower Yangtze River Basin Type, the Southwest Type, the Plateau Type, and the remainder of the Central China Type. Eight haplotypes and two recombination sites were identified within a conserved 40.09 Mb linkage-disequilibrium (LD) block on the X chromosome. Potential candidate genes (LEPR, FANCC, COL1A1, and PCCA) influencing body size were identified. Our findings provide insights into the phylogeny of Chinese indigenous pig breeds and benefit gene mining efforts to improve major economic traits. [ABSTRACT FROM AUTHOR]

The positive regulatory domain containing 16 (PRDM16) gene is a dominant transcriptional regulator that favors the "browning" of white adipocytes in rodents. Since the "browning" of white fat is important in pig in terms of producing heat fighting against cold environment, avoiding obesity, and improving meat quality, understanding the critical role that PRDM16 gene played in pig adipose "browning" and energy metabolism is of great significance. However, the constitution of pig fat differs a lot from rodents and human as they do not have brown adipose tissue (BAT) even in the newborn piglets. In this study, we isolated porcine primary preadipocytes and investigated the function of PRDM16 during preadipocytes differentiation. Our results showed that overexpression of the PR domain of PRDM16 repressed the differentiation of porcine preadipocytes, indicated by oil red O staining and the deposition of the triglyceride. Overexpression of the PR domain significantly increased the level of lipolysis and mitochondrial oxidative capacity detected by Western blotting during differentiation. Furthermore, we purified the protein coded by the PR domain and demonstrated that this protein has the H3K9me1 methyltransferase activity. In conclusion, the PR domain of the porcine PRDM16 gene repressed the mature of the porcine preadipocytes by promoting its oxidative activity. [ABSTRACT FROM AUTHOR]

Abstract Pig is a useful medical model for humans due to its similarity in size and physiology. Skeletal muscle plays an essential role in body movement. However, the skeletal muscle injuries are common. Skeletal muscle function maintenance largely depends on preserving the regenerative capacity of muscle. Muscle satellite cells proliferation plays an essential role in postnatal muscle growth and regeneration. Therefore, understanding the mechanisms associated with muscle satellite cells proliferation is essential for devising the alternative treatments for muscle injury. Previous studies showed JAG1-Notch1 signaling pathway and miRNAs regulate the skeletal muscle development. JAG1-Notch1 signal pathway regulates the transcription of certain types of miRNAs which further affects target gene expression. However, the specific relationship between JAG1-Notch1 signal pathway and miRNAs during muscle development has not been established. We found overexpression of intracellular domain of the Notch1 protein (N1ICD) in porcine muscle satellite cells (PSCs) decreased miR-199b level. We demonstrated that miR-199b inhibits PSCs proliferation using the overexpression and inhibition of miR-199b experiment. We also found JAG1, the miR-199b target gene, promotes PSCs proliferation through activating the Notch1 signal pathway. Furthermore, we demonstrated miR-199b forms a feedback loop with the JAG1-Notch1 signal pathway to maintain the PSCs niche homeostasis. Our results of miRNAs and genes work collaboratively in regulating PSCs proliferation expand our understanding in PSCs proliferation mechanism. Furthermore, this finding indicates miR-199b is a potential therapeutic target for muscle atrophy. Highlights • Overexpressing N1ICD decreases miR-199b level in porcine muscle satellite cells. • MiR-199b represses porcine muscle satellite cells proliferation by targeting JAG1. • MiR-199b forms a feedback loop with JAG1-Notch1 signal pathway. • MiR-199b is a potential therapeutic target for muscle atrophy. [ABSTRACT FROM AUTHOR]

Background/Aims: Brown adipose tissue (BAT) is critical for mammals’ survival in the cold environment. BAT-dependent non-shivering thermogenesis is attributed to uncoupling protein 1 (UCP1)’s disengagement of oxidative phosphorylation from ATP synthesis and dissipates energy as heat. Thus individuals with a substantial amount of BAT are better equipped during cold stress and less likely to become obese. Recently, our laboratory has shown pig adipocytes have no UCP1 protein. The inability of newborn piglets to generate heat contributed to its high death rate. Repairing the genetic defect of UCP1 in pig adipocytes has implications in defending against cold for piglets and developing an alternative treatment for human obesity. Methods: Q-PCR, western blotting (WB) and oxygen consumption measurement were used to enable functional UCP1 protein in preadipocytes. Immunoprecipitation (IP), chromatin immunoprecipitation (CHIP), and dual-luciferase reporter assay system were used to clarify the thermogenesis mechanism of functional UCP1. Results: Only co-overexpressing mice UCP1 and pig PGC-1α increased not only the mitochondrial number but also the uncoupled respiration rate in the transfected pig adipocytes. The functional mice UCP1 increased the pig PGC-1α activity through the AMPK-SIRT1 pathway. The active form PGC-1α interacted with transcription factors Lhx8, Zic1, ERRα, and PPARα to regulate the expression of mitochondrial energy metabolism and adipocytes browning-related genes. Conclusion: Our data suggest a model in which pig PGC-1α and mice UCP1 work collaboratively to restore uncoupling respiration in pig preadipocytes. These results have great implications for piglet survival and developing an alternative treatment for human obesity in the future. [ABSTRACT FROM AUTHOR]

Brown adipose tissue (BAT) is critical for mammal's survival in the cold environment. Uncoupling protein 1 (UCP1) is responsible for the non-shivering thermogenesis in the BAT. Pig is important economically as a meat-producing livestock. However, whether BAT or more precisely UCP1 protein exists in pig remains a controversy. The objective of this study was to ascertain whether pig has UCP1 protein. In this study, we used rapid amplification of cDNA ends (RACE) technique to obtain the UCP1 mRNA 3′ end sequence, confirmed only exons 1 and 2 of the UCP1 gene are transcribed in the pig. Then we cloned the pig UCP1 gene exons 1 and 2, and expressed the UCP1 protein from the truncated pig gene using E. coli BL21. We used the expressed pig UCP1 protein as antigen for antibody production in a rabbit. We could not detect any UCP1 protein expression in different pig adipose tissues by the specific pig UCP1 antibody, while our antibody can detect the cloned pig UCP1 as well as the mice adipose UCP1 protein. This result shows although exons 1 and 2 of the pig UCP1 gene were transcribed but not translated in the pig adipose tissue. Furthermore, we detected no uncoupled respiration in the isolated pig adipocytes. Thus, these results unequivocally demonstrate that pig has no UCP1 protein. Our results have resolved the controversy of whether pigs have the brown adipose tissue. [ABSTRACT FROM AUTHOR]

We read with interest the article by Song et al,[1] who revealed that endogenous microRNA-210 protects heart function in myocardial infarction through a compensatory manner. microRNA-210 targeting mitochondrial GPD2 (glycerol-3-phosphate dehydrogenase) controls mitochondrial bioenergetics, reactive oxygen species flux, and cardiomyocyte energy in the setting of heart ischemia-reperfusion (IR) injury. The authors should display the results of cardiac GPD2 changes in wild-type and microRNA-210 knockout female mice after IR treatment. If the cardiac GPD2 does not change in female mice with IR treatment, this indicates that there is no targeting relationship between microRNA-210 and GPD2 in the female mice. [Extracted from the article]

Abstract: Series new Ba4RETiNb9O30 (RE=La, Pr, Nd, Sm, Eu, Gd) compounds and ceramics were prepared by solid state reaction method respectively. The phase structure, microstructure, dielectric and ferroelectric properties of obtained ceramics were systematically investigated. The XRD results show that all ceramics have been determined as pure tungsten bronze phase. The dielectric characterization indicates that the former four ceramics are relaxors with strong diffuse phase transition and frequency dispersion, while the latter two ceramics show diffuse phase transition. Phase transition temperatures and tetragonality of tungsten bronze structure increase with the decrease of the radii of rare earth. All ceramics have ferroelectricity, among them Ba4GdTiNb9O30 has the highest remnant polarization (2Pr) of 5.12μC/cm2. [Copyright &y& Elsevier]

Skeletal muscle plays a crucial role in physical activity and in regulating body energy and protein balance. Myoblast proliferation, differentiation, and apoptosis are indispensable processes for myoblast myogenesis. Profilin 2a (PFN2a) is a ubiquitous actin monomer-binding protein and promotes lung cancer growth and metastasis through suppressing the nuclear localization of histone deacetylase 1 (HDAC1). However, how PFN2a regulates myoblast myogenic development is still not clear. We constructed a C2C12 mouse myoblast cell line overexpressing PFN2a. The CRISPR/Cas9 system was used to study the function of PFN2a in C2C12 myogenic development. We find that PFN2a suppresses proliferation and promotes apoptosis and consequentially downregulates C2C12 myogenic development. The suppression of PFN2a also decreases the amount of HDAC1 in the nucleus and increases the protein level of p53 during C2C12 myogenic development. Therefore, we propose that PFN2a suppresses C2C12 myogenic development via the p53 pathway. Si-p53 (siRNA-p53) reverses the PFN2a inhibitory effect on C2C12 proliferation and the PFN2a promotion effect on C2C12 apoptosis, and then attenuates the suppression of PFN2a on myogenic differentiation. Our results expand understanding of PFN2a regulatory mechanisms in myogenic development and suggest potential therapeutic targets for muscle atrophy-related diseases. [ABSTRACT FROM AUTHOR]

Skeletal muscle plays an essential role in maintaining body energy homeostasis and body flexibility. Loss of muscle mass leads to slower wound healing and recovery from illness, physical disability, poor quality of life, and higher health care costs. So, it is critical for us to understand the mechanism of skeletal muscle myogenic differentiation for maintaining optimal health throughout life. miR-501-3p is a novel muscle-specific miRNA, and its regulation mechanism on myoblast myogenic differentiation is still not clear. We demonstrated that FOS was a direct target gene of miR-501-3p, and MyoD regulated miR-501-3p host gene Clcn5 through bioinformatics prediction. Our previous laboratory experiment found that MDFI overexpression promoted C2C12 myogenic differentiation and MyoD expression. The database also showed there is an FOS binding site in the MDFI promoter region. Therefore, we hypothesize that miR-501-3p formed a feedback loop with FOS, MDFI, and MyoD to regulate myoblast differentiation. To validate our hypothesis, we demonstrated miR-501-3p function in the proliferation and differentiation period of C2C12 cells by transfecting cells with miR-501-3p mimic and inhibitor. Then, we confirmed there is a direct regulatory relationship between miR-501-3p and FOS, MyoD and miR-501-3p, FOS and MDFI through QPCR, dual-luciferase reporter system, and ChIP experiments. Our results not only expand our understanding of the muscle myogenic development mechanism in which miRNA and genes participate in controlling skeletal muscle development, but also provide treatment strategies for skeletal muscle or metabolic-related diseases in the future. [ABSTRACT FROM AUTHOR]

Novel Ba4LnTiNb9O30 compounds with Ln: La, Pr, Nd, Sm, Eu, and Gd are prepared by solid state reaction of stoichiometric mixtures of CaCO3, Ln2O3, TiO2, and Nb2O5 (1300 °C, 8 h, followed by sintering at 1290-1380 °C for 8 h). [ABSTRACT FROM AUTHOR]

Atherosclerosis is a chronic inflammatory disease characterized by innate and adaptive immune responses, which seriously threatens human life and health. It is a primary cause of coronary heart disease, myocardial infarction, and peripheral vascular disease. Research has demonstrated that immune cells are fundamental to the development of atherosclerosis and chronic inflammation. Therefore, it is anticipated that immunotherapy targeting immune cells will be a novel technique in the management of atherosclerosis. This article reviews the growth of research on the regulatory role of immune cells in atherosclerosis and targeted therapy approaches. The purpose is to offer new therapeutic approaches for the control and treatment of cardiovascular illnesses caused by atherosclerosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Liu, Chen, Hou, Yu, Ma, Jiang and Zhao.)

Ginsenoside Rb1 is the major active constituent of ginseng, which is widely used in traditional Chinese medicine for the atherosclerosis treatment by anti-inflammatory, anti-oxidant and reducing lipid accumulation. We explored cellular target and molecular mechanisms of ginsenoside Rb1 based on network pharmacology and in vitro experimental validation. In this study, we predicted 17 potential therapeutic targets for ginsenoside Rb1 with atherosclerosis from public databases. We then used protein-protein interaction network to screen the hub targets. Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway enrichment showed that the effects of ginsenoside Rb1 were meditated through multiple targets and pathways. Next, molecular docking results revealed that in the 10 core targets, CCND1 has the highest binding energy with ginsenoside Rb1. Vascular cell proliferation plays a critical role in atherosclerosis development. However, the effect and direct target of ginsenoside Rb1 in regulating vascular cell proliferation in atherosclerosis remains unclear. Edu straining results indicated that ginsenoside Rb1 inhibited the cell proliferation of endothelial cells, macrophages, and vascular smooth muscle cells. The protein immunoprecipitation (IP) analysis showed that ginsenoside Rb1 inhibited the vascular cell proliferation by suppressing the interaction of CCDN1 and CDK4. These findings systematically reveal that the anti-atherosclerosis mechanism of ginsenoside Rb1 by integrating network pharmacology and experimental validation, which provide evidence to treat atherosclerosis by using ginsenoside Rb1 and targeting CCND1.

Lysine crotonylation is a newly identified posttranslational modification that is different from the widely studied lysine acetylation in structure and function. In the last dozen years, great progress has been made in lysine crotonylation-related studies, and lysine crotonylation is involved in reproduction, development, and disease. In this review, we highlight the similarities and differences between lysine crotonylation and lysine acetylation. We also summarize the methods and tools for the detection and prediction of lysine crotonylation. At the same time, we outline the recent advances in understanding the mechanisms of enzymatic and metabolic regulation of lysine crotonylation, as well as the regulating factors that selectively recognize this modification. Particularly, we discussed how dynamic changes in crotonylation status maintain physiological health and result in the development of disease. This review not only points out the new functions of lysine crotonylation but also provides new insights and exciting opportunities for managing various diseases., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Lipid accumulation in macrophages plays an important role in atherosclerosis and is the major cause of atherosclerotic cardiovascular disease. Reducing lipid accumulation in macrophages is an effective therapeutic target for atherosclerosis. Insulin-like growth factor 1 (IGF-1) exerts the anti-atherosclerotic effects by inhibiting lipid accumulation in macrophages. Furthermore, almost all circulating IGF-1 combines with IGF binding proteins (IGFBPs) to activate or inhibit the IGF signaling. However, the mechanism of IGFBPs in macrophage lipid accumulation is still unknown. GEO database analysis showed that among IGFBPS family members, IGFBPL1 has the largest expression change in unstable plaque. We found that IGFBPL1 was decreased in lipid-laden THP-1 macrophages. Through oil red O staining, NBD-cholesterol efflux, liver X receptor α (LXRα) transcription factor and IGR-1 receptor blocking experiments, our results showed that IGFBPL1 inhibits lipid accumulation in THP-1 macrophages through promoting ABCG1-meditated cholesterol efflux, and IGFBPL1 regulates ABCG1 expression and macrophage lipid metabolism through IGF-1R/LXRα pathway. Our results provide a theoretical basis of IGFBPL1 in the alternative or adjunct treatment options for atherosclerosis by reducing lipid accumulation in macrophages.

Background: Astragalus mongholicus polysaccharides (APS) have anti-inflammatory, antioxidant and immunomodulatory effects. Recent studies have demonstrated the epigenetic regulation of N6-methyladenosine (m 6 A) in the development of inflammation. However, the effect of APS on m 6 A modification is unclear. Here, for the first time, we investigate the mechanism of m 6 A modification in APS regulation of THP-1 macrophage inflammation. Methods: We treated LPS-induced THP-1 macrophages with APS at different concentrations and times, and detected IL-6 mRNA and protein levels by quantitative real-time PCR (qRT-PCR) and western blot, respectively. The m 6 A modification level was detected by m 6 A quantification kit. The proteins that regulate m 6 A modification were screened by western blot. Wilms' tumor 1-associating protein (WTAP) was overexpressed in APS-treated THP-1 macrophages and the m 6 A modification level and IL-6 expressions were detected. Results: These findings confirmed that APS significantly abolished LPS-induced IL-6 levels in THP-1 macrophages. Meanwhile, APS reduced m 6 A modification levels and WTAP gene expression in THP-1 macrophages. Further overexpression of WTAP can significantly reverse APS-induced m 6 A modification level and IL-6 expression. Mechanistically, APS regulates IL-6 expression through WTAP-mediated p65 nuclear translocation. Conclusion: Overall, our study suggested that WTAP mediates the anti-inflammatory effect of APS by regulating m 6 A modification levels in THP-1 macrophages. This study reveals a new dimension of APS regulation of inflammation at the epigenetic level., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Long, Lin, Zheng, Hou, Zhang, Lin, Yin and Zhao.)

Intestinal epithelial cells are critical for nutrient absorption and defending against pathogen infection. Deoxynivalenol (Don), the most common mycotoxin, contaminates cereals and food throughout the world, causes serious damage to mammal intestinal mucosa, and appears as intestinal epithelial cell apoptosis and proliferation inhibition. Our previous study has found that milk-derived exosome ameliorates Don-induced intestinal damage, but the mechanism is still not fully understood. In this study, we demonstrated that Don downregulated the expression of miR-221/222 in intestinal epithelial cells, and exosome treatment reversed the inhibitory effect of Don on miR-221/222. Through immunofluorescence and flow cytometry analysis, we identified that miR-221/222 ameliorates Don-induced apoptosis and proliferation inhibition in intestinal epithelial cells. Through bioinformatics analyses and RNA immunoprecipitation analysis, we identified Phosphatase and tensin homolog (PTEN) is the target of miR-221/222. Through the PTEN interfering experiment, we found Don-induced apoptosis and proliferation inhibition relied on PTEN. Finally, through adenovirus to overexpress miR-221/222 in mice intestinal epithelial cells specifically, our results showed that miR-221/222 ameliorated Don-induced apoptosis and proliferation inhibition in intestinal epithelial cells by targeting PTEN. This study not only expands our understanding of how miR-221/222 and the host gene PTEN regulate intestinal epithelial cells defending against Don-induced damage, but also provides a new way to protect the development of the intestine., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hou, Tong, Lin, Yu, Ye and Xie.)

This study aims to study the protective effect and mechanism of carnosol on intestinal oxidative stress. Porcine intestinal epithelial cells (ZYM-SIEC02) were pretreated with carnosol. Tert-butyl hydroperoxide (t-BHP) was added to stimulate the cells. The cell colonization and viability were detected by Edu staining, MTT, and cell counting kit-8 (CCK8) assays. The expressions of reactive oxygen species (ROS), nitric oxide (NO), superoxide dismutase (SOD), and malondialdehyde (MDA) in intracellular and oxidative stress were detected. The expression of related genes and proteins in cells was detected by real-time PCR and western blot. The regulatory mechanisms were identified by co-immunoprecipitation (Co-IP) and chromatin immunoprecipitation (CHIP) assays. The results showed that t-BHP reduced cell proliferation and viability, while cells pretreated with carnosol had resistance to t-BHP, decreased intracellular ROS, MDA and NO levels, and increased SOD content. The mRNA and protein levels of heme oxygenase 1/Nuclear respiratory factor 2 (HO-1/Nrf-2) in ZYM-SIEC02 cells treated with carnosol were significantly increased. Nrf2 was able to bind to cell cycle negative regulatory protein p21 Nrf2 could bind to the promoter regions of cyclin D1 ( CCND1 ) and SOD genes. In conclusion, carnosol has a protective effect on intestinal epithelial cells by up-regulating the expression of Nrf2 and inhibiting p21 protein to promote the expression of CCND1 and SOD., Competing Interests: None., (IJCEP Copyright © 2020.)

Background/aims: Skeletal muscle plays an essential role in the body movement. However, injuries to the skeletal muscle are common. Lifelong maintenance of skeletal muscle function largely depends on preserving the regenerative capacity of muscle. Muscle satellite cells proliferation, differentiation, and myoblast fusion play an important role in muscle regeneration after injury. Therefore, understanding of the mechanisms associated with muscle development during muscle regeneration is essential for devising the alternative treatments for muscle injury in the future., Methods: Edu staining, qRT-PCR and western blot were used to evaluate the miR-27b effects on pig muscle satellite cells (PSCs) proliferation and differentiation in vitro. Then, we used bioinformatics analysis and dual-luciferase reporter assay to predict and confirm the miR-27b target gene. Finally, we elucidate the target gene function on muscle development in vitro and in vivo through Edu staining, qRT-PCR, western blot, H&E staining and morphological observation., Result: miR-27b inhibits PSCs proliferation and promotes PSCs differentiation. And the miR-27b target gene, MDFI, promotes PSCs proliferation and inhibits PSCs differentiation in vitro. Furthermore, interfering MDFI expression promotes mice muscle regeneration after injury., Conclusion: our results conclude that miR-27b promotes PSCs myogenesis by targeting MDFI. These results expand our understanding of muscle development mechanism in which miRNAs and genes work collaboratively in regulating skeletal muscle development. Furthermore, this finding has implications for obtaining the alternative treatments for patients with the muscle injury., (© 2018 The Author(s). Published by S. Karger AG, Basel.)

Since pork accounts for about 40% of global meat consumption, the pig is an important economic animal for meat production. Pig is also a useful medical model for humans due to its similarity in size and physiology. Understanding the mechanism of muscle development has great implication for animal breeding and human health. Previous studies showed porcine muscle satellite cells (PSCs) are important for postnatal skeletal muscle growth, and Notch1 signaling pathway and miRNAs regulate the skeletal muscle development. Notch1 signal pathway regulates the transcription of certain types of miRNAs which further affects target gene expression. However, the specific relationship between Notch1 and miRNAs during muscle development has not been established. We found miR-34c is decreased in PSCs overexpressed N1ICD. Through the overexpression and inhibition of mi-34c, we demonstrated that miR-34c inhibits PSCs proliferation and promotes PSCs differentiation. Using dual-luciferase reporter assay and Chromatin immunoprecipitation, we demonstrate there is a reciprocal regulatory loop between Notch1 and miR-34c. Furthermore, injection of miR-34c lentivirus into mice caused repression of gastrocnemius muscle development. In summary, our data revealed that miR-34c can form a regulatory loop with Notch1 to repress muscle development, and this result expands our understanding of muscle development mechanism.