A role for condensin-mediator interaction in mitotic chromosomal organization.

Eukaryotic genomes are organized by condensin into 3D chromosomal architectures suitable for chromosomal segregation during mitosis. However, molecular mechanisms underlying the condensin-mediated chromosomal organization remain largely unclear. Here, we investigate the role of newly identified interaction between the Cnd1 condensin and Pmc4 mediator subunits in fission yeast, Schizosaccharomyces pombe. We develop a condensin mutation, cnd1-K658E, that impairs the condensin-mediator interaction and find that this mutation diminishes condensinmediated chromatin domains during mitosis and causes chromosomal segregation defects. The condensin-mediator interaction is involved in recruiting condensin to highly transcribed genes and mitotically activated genes, the latter of which demarcate condensin-mediated domains. Furthermore, this study predicts that mediator-driven transcription of mitotically activated genes contributes to forming domain boundaries via phase separation. This study provides a novel insight into how genome-wide gene expression during mitosis is transformed into the functional chromosomal architecture suitable for chromosomal segregation.

The effect of matrine and glycyrrhizic acid on porcine reproductive and respiratory syndrome virus in Vitro and in vivo.

Porcine reproductive and respiratory syndrome (PRRS) is endemic worldwide, seriously affecting the development of the pig industry, but vaccines have limited protective effects against PRRSV transmission. The aim of this study was to identify potential anti-PRRSV drugs. We examined the cytotoxicity of seven compounds formulated based on the mass ratio of glycyrrhizic acid to matrine and calculated their inhibition rates against PRRSV in vitro. The results showed that the seven compounds all had direct killing and therapeutic effects on PRRSV, and the compounds inhibited PRRSV replication in a time- and dose-dependent manner. The compound with the strongest anti-PRRSV effect was selected for subsequent in vivo experiments. Pigs were divided into a control group and a medication group for the in vivo evaluation. The results showed that pigs treated with the 4:1 compound had 100% morbidity after PRRSV challenge, and the mortality rate reached 75% on the 8th day of the virus challenge. These results suggest that this compound has no practical anti-PRRSV effect in vivo and can actually accelerate the death of infected pigs. Next, we further analyzed the pigs that exhibited semiprotective effects following vaccination with the compound to determine whether the compound can synergize with the vaccine in vivo. The results indicated that pigs treated with the compound had higher mortality rates and more severe clinical reactions after PRRSV infection (p < 0.05). The levels of proinflammatory cytokines (IL-6, IL-8, IL-1ß, IFN-γ, and TNF-α) were significantly greater in the compound-treated pigs than in the positive control-treated pigs (p < 0.05), and there was no synergistic enhancement with the live attenuated PRRSV vaccine (p < 0.05). The compound enhanced the inflammatory response, prompted the body to produce excessive levels of inflammatory cytokines and caused body damage, preventing a therapeutic effect. In conclusion, the present study revealed that the in vitro effectiveness of these agents does not indicate that they are effective in vivo or useful for developing anti-PRRSV drugs. Our findings also showed that, to identify effective anti-PRRSV drugs, comprehensive drug screening is needed, for compounds with solid anti-inflammatory effects both in vitro and in vivo. Our study may aid in the development of new anti-PRRSV drugs.

Efficacy and safety of transanal opening of intersphincteric space in the treatment of high complex anal fistula: A meta­analysis.

The best treatment of high complex anal fistula (HCAF) is to avoid anal incontinence while improving the cure rate. On this basis, several surgical procedures for preserving the anal sphincter have been proposed. The purpose of the present study was to evaluate the efficacy and safety of transanal opening of intersphincteric space for treating HCAF. PubMed, Cochrane Library, China National Knowledge Infrastructure and the Wanfang databases were searched to collate all the articles on transanal opening of intersphincteric space for treating HCAF. A total of two researchers independently completed the whole process, from screening and inclusion to data extraction and the data was included in the RevMan 5.3 software for analysis. The main outcomes included the patients' essential characteristics, primary healing rate, management after recurrence, final healing rate, anal incontinence score before and after surgery, postoperative complication rate and types of complications. A total of six articles were included in this meta-analysis. The results showed that the weighted final healing rate of patients following transanal opening of intersphincteric space was 89% [risk differences (RD)=0.89; 95% confidence interval (CI)=0.86-0.92; I2=0%; P<0.00001]. The results of the anal incontinence score showed that there was no significant difference between the results before and after transanal opening of intersphincteric space surgery mean differences [(MD)=-0.04, Cl=-0.10-0.02, I2=0%; P=0.21]. Only 11 patients were reported to have complications, including urinary retention and bleeding following transanal opening of intersphincteric space with a complication rate of 8% (11/138) and the weighted average complication rate was 6% (RD=0.06,95% CI=0.02-0.10; I2=9%; P=0.003). Transanal opening of intersphincteric space has a high cure rate, a favorable anal incontinence score, fewer types of postoperative complications and a low complication rate; it can be used as a minimally invasive and sphincter-preserving surgical method for treating HCAF and is worthy of further promotion and research in clinical practice.

Sensitive and reliable hybrid nanosensor (Co2+-CDs@R-CDs) for ratiometric fluorescent and colorimetric detecting NO2.

A ratiometric fluorescent and colorimetric detecting assay for NO2- was realized by a hybrid nanosensor (Co2+-CDs@R-CDs) utilizing firstly through the redox reaction of nitrite (NO2-) with Co2+, of which the hybrid nanosensor Co2+-CDs@R-CDs was fabricated by Co2+-doped carbon dots (Co2+-CDs) and a reference of red-emitting carbon dots (R-CDs). The ratiometric fluorescent linear detection range of NO2- was 2.5-45 µM and the limit of detection (LOD) was 0.068 µM with the response time of 120 s. While, the colorimetric linear detection range of NO2- was 2.5-60 µM and the LOD was 0.075 µM. In addition, a portable smartphone system which could measure the R (red), G (green), and B (blue) values of the fluorescence and the visible color of the coated Co2+-CDs@R-CDs paper strip-based sensor had also been developed and successfully applied to detect NO2- in sausage, pickles and tap water samples.

The role of gut microbiota in anorexia induced by T-2 toxin.

T-2 toxin is one of trichothecene mycotoxins, which can impair appetite and decrease food intake. However, the specific mechanisms for T-2 toxin-induced anorexia are not fully clarified. Multiple research results had shown that gut microbiota have a significant effect on appetite regulation. Hence, this study purposed to explore the potential interactions of the gut microbiota and appetite regulate factors in anorexia induced by T-2 toxin. The study divided the mice into control group (CG, 0 mg/kg BW T-2 toxin) and T-2 toxin-treated group (TG, 1 mg/kg BW T-2 toxin), which oral gavage for 4 weeks, to construct a subacute T-2 toxin poisoning mouse model. This data proved that T-2 toxin was able to induce an anorexia in mice by increased the contents of gastrointestinal hormones (CCK, GIP, GLP-1 and PYY), neurotransmitters (5-HT and SP), as well as pro-inflammatory cytokines (IL-1ß, IL-6 and TNF-α) in serum of mice. T-2 toxin disturbed the composition of gut microbiota, especially, Faecalibaculum and Allobaculum, which was positively correlated with CCK, GLP-1, 5-HT, IL-1ß, IL-6 and TNF-α, which played a certain role in regulating host appetite. In conclusion, gut microbiota changes (especially an increase in the abundance of Faecalibaculum and Allobaculum) promote the upregulation of gastrointestinal hormones, neurotransmitters, and pro-inflammatory cytokines, which may be a potential mechanism of T-2 toxin-induced anorexia.

Machine learning-enhanced molecular network reveals global exposure to hundreds of unknown PFAS.

Unknown forever chemicals like per- and polyfluoroalkyl substances (PFASs) are difficult to identify. Current platforms designed for metabolites and natural products cannot capture the diverse structural characteristics of PFAS. Here, we report an automatic PFAS identification platform (APP-ID) that screens for PFAS in environmental samples using an enhanced molecular network and identifies unknown PFAS structures using machine learning. Our networking algorithm, which enhances characteristic fragment matches, has lower false-positive rate (0.7%) than current algorithms (2.4 to 46%). Our support vector machine model identified unknown PFAS in test set with 58.3% accuracy, surpassing current software. Further, APP-ID detected 733 PFASs in real fluorochemical wastewater, 39 of which are previously unreported in environmental media. Retrospective screening of 126 PFASs against public data repository from 20 countries show PFAS substitutes are prevalent worldwide.

Effects of Se-enriched yeast on the amelioration of atrazine-induced meat quality degradation.

Atrazine (ATR) is herbicide that causes serious harm to the environment and threatens human food safety. Se-enriched yeast is the best organic selenium source for protecting cells from damage caused by poisonous substances. To explore mechanism of ATR on meat quality degradation and potential protective effects of Se-enriched yeast on ATR-induced muscle injury, quails were treated with ATR and/or Se-enriched yeast for 28 days. The results found ATR disrupted muscle fiber structure and decreased pH, tenderness, water-holding capacity, essential amino acid content and polyunsaturated fatty acid content. ATR aggravated oxidative stress and inflammation by inhibiting Nrf2 pathway and activating NF-κB pathway, ultimately causing apoptosis. However, Se-enriched yeast alleviated ATR-induced alterations in muscle chemical and physical properties by inhibiting oxidative stress and inflammation. Taken together, these results revealed that ATR exposure caused meat quality degradation and Se-enriched yeast had the potential to counteract ATR-induced myotoxicity by inhibiting oxidative stress and inflammation.

Forsythiaside A attenuates lipopolysaccharide-induced mouse mastitis by activating autophagy and regulating gut microbiota and metabolism.

Mastitis is an inflammatory disease of the mammary gland with a high incidence in lactating animals, significantly impacting their health and breastfeeding. Moreover, mastitis adversely affects milk quality and yield, resulting in substantial economic losses for the dairy farming industry. Forsythiaside A (FTA), a phenylethanol glycoside analog extracted from Forsythia, exhibits notable anti-inflammatory and antioxidant properties. However, its protective effects and specific mechanisms against mastitis remain unclear. In this study, a lipopolysaccharide (LPS)-induced mouse mastitis model was used to investigate the protective effect of FTA on LPS-induced mastitis and its potential mechanism using histological assays, Western blot, qRT-PCR, FITC-albumin permeability test, 16s rRNA gene sequencing analysis and non-targeted metabolomics assays to investigate the protective effect of FTA on LPS-induced mastitis model and its potential mechanism. The results demonstrated that FTA significantly mitigated LPS-induced mouse mastitis by reducing inflammation and apoptosis levels, modulating the PI3K/AKT/mTOR signaling pathways, inducing autophagy, and enhancing antioxidant capacity and the expression of tight junction proteins. Furthermore, FTA increased the abundance of beneficial microbiota while decreasing the levels of harmful microbiota in mice, thus counteracting the gut microbiota disruption induced by LPS stimulation. Intestinal metabolomics analysis revealed that FTA primarily regulated LPS-induced metabolite alterations through key metabolic pathways, such as tryptophan metabolism. This study confirms the anti-inflammatory and antioxidant effects of FTA on mouse mastitis, which are associated with key metabolic pathways, including the restoration of gut microbiota balance and the regulation of tryptophan metabolism. These findings provide a novel foundation for the treatment and prevention of mammalian mastitis using FTA.

Chemo-Senolytic Therapeutic Potential against Angiosarcoma.

Angiosarcoma is an aggressive soft-tissue sarcoma with a poor prognosis. Chemotherapy for this cancer typically employs paclitaxel, a taxane (genotoxic drug), although it has a limited effect owing to chemoresistance to prolonged treatment. In this study, we examine an alternative angiosarcoma treatment approach that combines chemotherapeutic and senolytic agents. We find that the chemotherapeutic drugs cisplatin and paclitaxel efficiently induce senescence in angiosarcoma cells. Subsequent treatment with the senolytic agent ABT-263 eliminates senescent cells by activating the apoptotic pathway. In addition, expression analysis indicates that senescence-associated secretory phenotype genes are activated in senescent angiosarcoma cells and that ABT-263 treatment downregulates IFN-I pathway genes in senescent cells. Moreover, we show that cisplatin treatment alone requires high doses to remove angiosarcoma cells. In contrast, lower doses of cisplatin are sufficient to induce senescence, followed by the elimination of senescent cells by the senolytic treatment. This study sheds light on a potential therapeutic strategy against angiosarcoma by combining a relatively low dose of cisplatin with the ABT-263 senolytic agent, which can help ease the deleterious side effects of chemotherapy.

Sprouty genes regulate activated fibroblasts in mammary epithelial development and breast cancer.

Stromal fibroblasts are a major stem cell niche component essential for organ formation and cancer development. Fibroblast heterogeneity, as revealed by recent advances in single-cell techniques, has raised important questions about the origin, differentiation, and function of fibroblast subtypes. In this study, we show in mammary stromal fibroblasts that loss of the receptor tyrosine kinase (RTK) negative feedback regulators encoded by Spry1, Spry2, and Spry4 causes upregulation of signaling in multiple RTK pathways and increased extracellular matrix remodeling, resulting in accelerated epithelial branching. Single-cell transcriptomic analysis demonstrated that increased production of FGF10 due to Sprouty (Spry) loss results from expansion of a functionally distinct subgroup of fibroblasts with the most potent branching-promoting ability. Compared to their three independent lineage precursors, fibroblasts in this subgroup are "activated," as they are located immediately adjacent to the epithelium that is actively undergoing branching and invasion. Spry genes are downregulated, and activated fibroblasts are expanded, in all three of the major human breast cancer subtypes. Together, our data highlight the regulation of a functional subtype of mammary fibroblasts by Spry genes and their essential role in epithelial morphogenesis and cancer development.

miR-122/PPARß axis is involved in hypoxic exercise and modulates fatty acid metabolism in skeletal muscle of obese rats.

Hypoxic exercise is an effective intervention for obesity, because it promotes weight loss by regulating fatty acid (FA) metabolism. The regulation of peroxisome proliferator-activated receptor ß (PPARß) by miR-122 may be involved in this process, but the detailed mechanisms are unknown. In order to address this issue, we probed how miR-122 affected the expression of factors associated with FA metabolism in skeletal muscle of obese rats undergoing hypoxic training. By injecting adeno-associated virus 9 containing miR-122 overexpression vector or miR-122 inhibitor into skeletal muscles of rats with a 4-week hypoxic exercise regimen, the miR-122 expression level can be regulated. Body composition and blood lipid levels were analyzed, and PPARß, carnitine palmitoyltransferase 1b (CPT1b), acetylCoA carboxylase 2 (ACC2), and FA synthase (FAS) mRNA and protein levels were evaluated using quantitative reverse transcription quantitative PCR(RT-qPCR) and Western blot analysis. We found that miR-122 overexpression increased low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) levels and decreased PPARß, ACC2, and FAS expression. Conversely, miR-122 inhibition decreased TG level, increased high-density lipoprotein cholesterol (HDL-C) level, and upregulated PPARß, ACC2, FAS, and CPT1b. These data indicated that the negative regulation of PPARß by miR-122 promotes FA metabolism by altering the levels of the factors related to FA metabolism in skeletal muscle of obese rat under hypoxic training, thus providing molecular-level insight into the beneficial effects of this intervention.

Therapeutic strategies targeting cellular senescence for cancer and other diseases.

Cellular senescence occurs in response to endogenous or exogenous stresses and is characterized by stable cell cycle arrest, alterations in nuclear morphology and secretion of proinflammatory factors, referred to as the senescence-associated secretory phenotype (SASP). An increase of senescent cells is associated with the development of several types of cancer and aging-related diseases. Therefore, senolytic agents that selectively remove senescent cells may offer opportunities for developing new therapeutic strategies against such cancers and aging-related diseases. This review outlines senescence inducers and the general characteristics of senescent cells. We also discuss the involvement of senescent cells in certain cancers and diseases. Finally, we describe a series of senolytic agents and their utilization in therapeutic strategies.

Overview of T-2 Toxin Enterotoxicity: From Toxic Mechanisms and Detoxification to Future Perspectives.

Fusarium species produce a secondary metabolite known as T-2 toxin, which is the primary and most harmful toxin found in type A trichothecenes. T-2 toxin is widely found in food and grain-based animal feed and endangers the health of both humans and animals. T-2 toxin exposure in humans and animals occurs primarily through food administration; therefore, the first organ that T-2 toxin targets is the gut. In this overview, the research progress, toxicity mechanism, and detoxification of the toxin T-2 were reviewed, and future research directions were proposed. T-2 toxin damages the intestinal mucosa and destroys intestinal structure and intestinal barrier function; furthermore, T-2 toxin disrupts the intestinal microbiota, causes intestinal flora disorders, affects normal intestinal metabolic function, and kills intestinal epidermal cells by inducing oxidative stress, inflammatory responses, and apoptosis. The primary harmful mechanism of T-2 toxin in the intestine is oxidative stress. Currently, selenium and plant extracts are mainly used to exert antioxidant effects to alleviate the enterotoxicity of T-2 toxin. In future studies, the use of genomic techniques to find upstream signaling molecules associated with T-2 enterotoxin toxicity will provide new ideas for the prevention of this toxicity. The purpose of this paper is to review the progress of research on the intestinal toxicity of T-2 toxin and propose new research directions for the prevention and treatment of T-2 toxin toxicity.

Integrated Analysis of Per- and Polyfluoroalkyl Substance Exposure and Metabolic Profiling of Elderly Residents Living near Industrial Plants.

Per- and polyfluoroalkyl substances (PFASs) are widely used in industrial production, causing potential health risks to the residents living around chemical industrial plants; however, the lack of data on population exposure and adverse effects impedes our understanding and ability to prevent risks. In this study, we performed screening and association analysis on exogenous PFAS pollutants and endogenous small-molecule metabolites in the serum of elderly residents living near industrial plants. Exposure levels of 11 legacy and novel PFASs were determined. PFOA and PFOS were major contributors, and PFNA, PFHxS, and 6:2 Cl-PFESA also showed high detection frequencies. Association analysis among PFASs and 287 metabolites identified via non-target screening was performed with adjustments of covariates and false discovery rate. Strongly associated metabolites were predominantly lipid and lipid-like molecules. Steroid hormone biosynthesis, primary bile acid biosynthesis, and fatty-acid-related pathways, including biosynthesis of unsaturated fatty acids, linoleic acid metabolism, α-linolenic acid metabolism, and fatty acid biosynthesis, were enriched as the metabolic pathways associated with mixed exposure to multiple PFASs, providing metabolic explanation and evidence for the potential mediating role of adverse health effects as a result of PFAS exposure. Our study achieved a comprehensive screening of PFAS exposure and associated metabolic profiling, demonstrating the promising application for integrated analysis of exposome and metabolome.

Unveiling intricate transformation pathways of emerging contaminants during wastewater treatment processes through simplified network analysis.

As the key stage for purifying wastewater, elimination of emerging contaminants (ECs) is found to be fairly low in wastewater treatment plants (WWTPs). However, less knowledge is obtained regarding the transformation pathways between various chemical structures of ECs under different treatment processes. This study unveiled the transformation pathways of ECs with different structures in 15 WWTPs distributed across China by simplified network analysis (SNA) we proposed. After treatment, the molecular weight of the whole component of wastewater decreased and the hydrophilicity increased. There are significant differences in the structure of eliminated, consistent and formed pollutants. Amino acids, peptides, and analogues (AAPAs) were detected most frequently and most removable. Benzenoids were refractory. Triazoles were often produced. The high-frequency reactions in different WWTPs were similar, (de)methylation and dehydration occurred most frequently. Different biological treatment processes performed similarly, while some advanced treatment processes differed, such as a significant increase of -13.976 (2HO reaction) paired mass distances (PMDs) in the chlorine alone process. Further, the common structural transformation was uncovered. 4 anti-hypertensive drugs, including irbesartan, valsartan, olmesartan, and losartan, were identified, along with 22 transformation products (TPs) of them. OH2 and H2O PMDs occurred most frequently and in 80.81 % of the parent-transformation product pairs, the intensity of the product was higher than parent in effluents, whose risk should be considered in future assessment activity. Together our results provide a macrography perspective on the transformation processes of ECs in WWTPs. In the future, selectively adopting wastewater treatment technology according to structures is conductive for eliminating recalcitrant ECs in WWTPs.

Maintaining the Mitochondrial Quality Control System Was a Key Event of Tanshinone IIA against Deoxynivalenol-Induced Intestinal Toxicity.

Deoxynivalenol (DON) is the one of the most common mycotoxins, widely detected in various original foods and processed foods. Tanshinone IIA (Tan IIA) is a fat-soluble diterpene quinone extracted from Salvia miltiorrhiza Bunge, which has multi-biological functions and pharmacological effects. However, whether Tan IIA has a protective effect against DON-induced intestinal toxicity is unknown. In this study, the results showed Tan IIA treatment could attenuate DON-induced IPEC-J2 cell death. DON increased oxidation product accumulation, decreased antioxidant ability and disrupted barrier function, while Tan IIA reversed DON-induced barrier function impairment and oxidative stress. Furthermore, Tan IIA dramatically improved mitochondrial function via mitochondrial quality control. Tan IIA could upregulate mitochondrial biogenesis and mitochondrial fusion as well as downregulate mitochondrial fission and mitochondrial unfolded protein response. In addition, Tan IIA significantly attenuated mitophagy caused by DON. Collectively, Tan IIA presented a potential protective effect against DON toxicity and the underlying mechanisms were involved in mitochondrial quality control-mediated mitophagy.

Forsythiaside A attenuates mastitis via PINK1/Parkin-mediated mitophagy.

BACKGROUND: Bovine mastitis is the most common animal production disease in the global dairy industry, which affects the health of dairy cows. When bovine mastitis occurs, the mitochondrial metabolism of breast tissue increases, and the relationship between inflammation and mitophagy has become a hot topic for many scholars. The abuse of antibiotics leads to the increase of resistance to bovine mastitis. FTA is one of the main effective components of Forsythia suspensa, which has anti-inflammatory, anti-infection, anti-oxidation and anti-virus pharmacological effects, and has broad application prospects in the prevention and treatment of bovine mastitis. However, the relationship between the anti-inflammatory effects of FTA and mitophagy is still unclear. PURPOSE: This study mainly explores the anti-inflammatory effect of FTA in bovine mastitis and the relationship between mitophagy. METHODS: MAC-T cells and wild-type mice were used to simulate the in vitro and in vivo response of mastitis. After the pretreatment with FTA, CsA inhibitors and siPINK1 were used to interfere with mitophagy, and the mitochondrial function impairment and the expression of inflammatory factors were detected. RESULTS: It was found that pre-treatment with FTA significantly reduced LPS induced inflammatory response and mitochondrial damage, while promoting the expression of mitophagy related factors. However, after inhibiting mitophagy, the anti-inflammatory effect of FTA was inhibited. CONCLUSION: This study is the first to suggest the relationship between the anti-inflammatory effect of FTA and mitophagy. PINK1/Parkin-mediated mitophagy is one of the ways that FTA protects MAC-T cells from LPS-induced inflammatory damage.

Review of neurotoxicity of T-2 toxin.

T-2 toxin is a representative trichothecene that is widely detected in corn, wheat and other grain feeds. T-2 toxin has stable physical and chemical properties, making it difficult to remove from food and feed. Hence, T-2 toxin has become an unavoidable pollutant in food for humans and animals. T-2 toxin can enter brain tissue by crossing the blood-brain barrier and leads to congestion, swelling and even apoptosis of neurons. T-2 toxin poisoning can directly lead to clinical symptoms (anti-feeding reaction and decline of learning and memory function in humans and animals). Maternal T-2 toxin exposure also exerted toxic effects on the central nervous system of offspring. Oxidative stress is the core neurotoxicity mechanism underlying T-2 toxin poison. Oxidative stress-mediated apoptosis, mitochondrial oxidative damage and inflammation are all involved in the neurotoxicity induced by T-2 toxin. Thus, alleviating oxidative stress has become a potential target for relieving the neurotoxicity induced by T-2 toxin. Future efforts should be devoted to revealing the neurotoxic molecular mechanism of T-2 toxin and exploring effective therapeutic drugs to alleviate T-2 toxin-induced neurotoxicity.

Tanshinone IIA protects intestinal epithelial cells from deoxynivalenol-induced pyroptosis.

Deoxynivalenol (DON) is the most common mycotoxin in food and feed, which can cause undesirable effects, including diarrhea, emesis, weight loss, and growth delay in livestock. Intestinal epithelial cells were the main target of DON, which can cause oxidative stress and inflammatory injury. Tanshinone IIA (Tan IIA) is fat-soluble diterpene quinone, which is the most abundant active ingredient in salvia miltiorrhiza plant with antioxidant and anti-inflammatory characteristics. However, it is not clear whether Tan IIA can protect against or inhibit intestinal oxidative stress and inflammatory injury under DON exposure. This study aimed to explore the protective effect of Tan IIA on DON-induced toxicity in porcine jejunum epithelial cells (IPEC-J2). Cells were exposed to 0, 0.5, 1.0, 2.0 µM DON and/or 45 µg/mL TAN ⅡA to detect oxidative stress indicators. inflammatory cytokines, NF-κB expression, NLRP3 inflammasome and pyroptosis-related factors. In this study, DON exposure caused IPEC-J2 cells oxidative stress by elevating ROS and 8-OHdG content, inhibited GSH-Px activity. Furthermore, DON increased pro-inflammatory factor (TNF-α, IL-1ß, IL-18 and IL-6) expression and decreased the anti-inflammatory factor (IL-10) expression, causing inflammatory response via triggering NF-κB pathway. Interestingly, above changes were alleviated after Tan IIA treatment. In addition, Tan IIA relieved DON-induced pyroptosis by suppressing the expression of pyroptosis-related factors (NLRP3, Caspase-1, GSDMD, IL-1ß, and IL-18). In general, our data suggested that Tan IIA can ameliorate DON-induced intestinal epithelial cells injury associated with suppressing the pyroptosis signaling pathway. Our findings pointed that Tan IIA could be used as the potential therapeutic drugs on DON-induced enterotoxicity.

Transcriptome sequencing analysis of bovine mammary epithelial cells induced by lipopolysaccharide.

Mastitis in cows is caused by the inflammation of the mammary glands due to an infection by external pathogenic bacteria. Mammary gland epithelial cells, which are in direct contact with the external environment, are responsible for the first line of defense of the mammary gland against pathogenic bacteria, playing an essential role in immune defense. To investigate the mechanism of bovine mammary epithelial cells in the inflammatory process, we treated the cells with LPS for 12 hours and analyzed the changes in mRNA by transcriptome sequencing. The results showed that compared to the control group, the LPS treatment group had 121 up-regulated genes and 18 down-regulated genes. GO and KEGG enrichment analysis revealed that these differential genes were mainly enriched in the IL-17 signaling pathway, Legionellosis, Cytokine-cytokine receptor interaction, NF-kappa B signaling pathway, and other signaling pathways. Furthermore, the expression of GRO1 and CXCL3 mRNAs increased significantly after LPS treatment. These findings provide new insights for the treatment of mastitis in cows in the future.