Green tea polyphenols inhibit TBBPA-induced lung injury via enhancing antioxidant capacity and modulating the NF-κB pathway in mice.

Tetrabromobisphenol A (TBBPA) is a global pollutant. When TBBPA is absorbed by the body through various routes, it can have a wide range of harmful effects on the body. Green tea polyphenols (GTPs) can act as antioxidants, resisting the toxic effects of TBBPA on animals. The effects and mechanisms of GTP and TBBPA on oxidative stress, inflammation and apoptosis in the mouse lung are unknown. Therefore, we established in vivo and in vitro models of TBBPA exposure and GTP antagonism using C57 mice and A549 cells and examined the expression of factors related to oxidative stress, autophagy, inflammation and apoptosis. The results of the study showed that the increase in reactive oxygen species (ROS) levels after TBBPA exposure decreased the expression of autophagy-related factors Beclin1, LC3-II, ATG3, ATG5, ATG7 and ATG12 and increased the expression of p62; oxidative stress inhibits autophagy levels. The increased expression of the pro-inflammatory factors IL-1ß, IL-6 and TNF-α decreased the expression of the anti-inflammatory factor IL-10 and activation of the NF-κB p65/TNF-α pathway. The increased expression of Bax, caspase-3, caspase-7 and caspase-9 and the decreased expression of Bcl-2 activate apoptosis-related pathways. The addition of GTP attenuated oxidative stress levels, restored autophagy inhibition and reduced the inflammation and apoptosis levels. Our results suggest that GTP can attenuate the toxic effects of TBBPA by modulating ROS, reducing oxidative stress levels, increasing autophagy and attenuating inflammation and apoptosis in mouse lung and A549 cells. These results provide fundamental information for exploring the antioxidant mechanism of GTP and further for studying the toxic effects of TBBPA.

High-fat diet disrupts the gut microbiome, leading to inflammation, damage to tight junctions, and apoptosis and necrosis in Nyctereutes procyonoides intestines.

Given the burgeoning Nyctereutes procyonoides breeding industry and its growing scale, it is imperative to investigate the impact of high-fat diets on the health of these animals. This study involved 30 male Nyctereutes procyonoides of comparable weights (3 kg ±0.5), randomly assigned to either a control group or a high-fat diet group (n = 15 each). The latter group was fed a mixture of lard and basal diet in a 2:5 ratio, establishing a high-fat diet model in Nyctereutes procyonoides. This diet induced diarrhea and histopathological changes in the Nyctereutes procyonoides. Analysis of the small intestine contents using 16S rRNA sequencing revealed a high-fat diet-induced disruption in the gut microbiota. Specifically, Escherichia-Shigella emerged as the biomarker in the high-fat diet group (P = 0.049), while Vagococcus was prevalent in the control group (P = 0.049), indicating a significant increase in harmful bacteria in the high-fat diet group. Furthermore, this disrupted gut flora correlated with inflammation and oxidative stress, as evidenced by marked increases in TNF-α (P < 0.01), IL-1ß (P < 0.05), and IL-6 (P < 0.05) levels, measured via q-PCR, Western blot, and oxidative stress assays. In addition, q-PCR analysis revealed significant upregulation of apoptosis and necrosis markers, including Bax, Caspase3, Caspase9, Caspase12, RIPK3, and RIPK1 (P < 0.01 to P < 0.001), and a concurrent downregulation of the anti-apoptotic gene Bcl-2 (P < 0.01) in the high-fat diet group, consistent with protein expression trends. These findings suggest that a high-fat diet alters the gut microbiome toward a more harmful bacterial composition, escalating inflammatory responses and intestinal tissue permeability, culminating in intestinal cell apoptosis and necrosis.IMPORTANCEThis study examines the impact of high-fat diets on Nyctereutes procyonoides. Our research established a Nyctereutes procyonoides model on a high-fat diet, revealing significant health impacts, such as diarrhea, histological anomalies, and alterations in the gut microbiota. These findings emphasize the importance of preventing health issues and promoting sustainable industry growth. They highlight the significant impact of diet on gut microbiota and overall animal health.

Polyethylene microplastics induced gut microbiota dysbiosis leading to liver injury via the TLR2/NF-κB/NLRP3 pathway in mice.

Microplastics (MPs) are ubiquitous environmental contaminants that have negative impacts on health and safety. The gut microbiota plays multiple roles as a newly discovered virtual metabolic organ. The objective of this study was to investigate the potential of MPs to cause liver injury by disrupting the balance of gut microbiota. The results indicated that exposure to MPs resulted in liver damage and disrupted the homeostasis of gut microbiota. MPs significantly reduced the liver organ coefficient, leading to liver cell injury and impaired function. Additionally, there was an increase in the expression of fibril-related proteins, which positively correlated with MPs concentration. Furthermore, MPs increased the relative abundances of Desulfovibrio, Clostridia, Enterorhabdus, Bacteroides, and Gemella while decreasing the abundance of Dubosoella. Different concentrations of MPs exhibited varying effects on specific bacterial groups, however, both concentrations resulted in an increase in pathogenic bacteria and a decrease in beneficial bacteria, as well as alterations in microbial structure. Moreover, MPs induced oxidative stress, inflammation, apoptosis and necrosis in liver cells. The study found that MPs disrupted gut microbiota homeostasis and activated TLR2/NF-κB/NLRP3 pathway in the liver, providing a new insight into the mechanism underlying MPs-induced liver injury. These findings serve as a warning regarding environmental pollution caused by MPs.

Tea polyphenols alleviate TBBPA-induced inflammation, ferroptosis and apoptosis via TLR4/NF-κB pathway in carp gills.

The extensive application of Tetrabromobisphenol A (TBBPA) leads to the pollution of part of the water environment and brings great safety risks to aquatic animals. As a natural extract, tea polyphenols (TPs) have antioxidant and anti-inflammatory effects. Gills are one of the immune organs of fish and constitute the first line of defense of the immune system. However, it was unclear whether TPs could mitigate TBBPA-induced gills injury. Therefore, an animal model was established to investigate the effect of TPs on TBBPA-induced gills. The results indicated that TBBPA changed the coefficient and tissue morphology of carp gills. In addition, TBBPA induced oxidative stress and inflammation, leading to ferroptosis and apoptosis in carp gills. Dietary addition of TPs significantly improved the antioxidant capacity of carp, effectively inhibited the overexpression of TLR4/NF-κB and its mediated inflammatory response. Moreover, TPs restored iron metabolism, reduced the expression of pro-apoptotic factors thereby alleviating ferroptosis and apoptosis in carp gills. This study enriched the protective effect of TPs and provided a new way to improve the innate immunity of carp.

Effectiveness of mandibular advancement devices in the treatment of obstructive sleep apnea and the impact of different body positions on treatment： A systematic review and meta-analysis.

OBJECTIVE: The meta-analysis aimed to evaluate the efficacy of mandibular advancement device (MAD) for the treatment of obstructive sleep apnea (OSA) and explore the effect of different positions on MAD for OSA. METHODS: The Embase, PubMed, Medline, and Cochrane Library databases were searched for relevant studies evaluating the effect of MAD on the treatment of OSA from database inception to November 2022. The Bayesian random-effects mode was used to calculate the pooled outcome. Subgroup analysis and sensitivity analysis were applied to investigate the heterogeneity. RESULTS: A total of 6 studies enrolling 643 patients were eligible for further analysis. MAD treatment led to improvements in total apnea-hypopnea index (AHI) for both positional OSA(POSA) and Non-POSA groups, but there was no significant difference in the effect of MAD on Non-POSA and POSA (MD = -1.46,95%CI [-4.89,1.97], P = 0.40). In the supine position, AHI improvement after MAD treatment in POSA group was more than that in Non-POSA group by 15 events/hour in average (MD = 14.82, 95%CI [11.43,18.22], P＜0.00001), while in the non-supine position, the change of AHI in Non-POSA group was significantly better than that in POSA group by approximately 8 events/hour (MD = -7.55,95%CI[-10.73,-4.38],p < 0.00001). CONCLUSION: MAD is more suitable for POSA compared to Non-POSA in patients with habitual sleep in the supine or supine predominant position. While for patients with habitual sleep in the non-supine position, MAD is an effective treatment option for Non-POSA.

Polyethylene microplastics cause apoptosis via the MiR-132/CAPN axis and inflammation in carp ovarian.

Microplastics (MPs) are widely distributed pollutants in the environment and accumulate in the aquatic environment due to human activities. Carp, a common edible aquatic organism, has been found to accumulate MPs in body. MicroRNA (miRNAs) is a non-coding short RNA that regulates protein expression by binding to target genes in various physiological processes such as proliferation, differentiation and apoptosis. The ovary is a crucial role in carp reproduction. In this study, we established a model of carp exposed to polyethylene microplastics (PE-MPs) in the aquatic environment to investigate the specific mechanism of PE-MPs causing ovarian injury and the involvement of miR-132/calpain (CAPN) axis. H&E stained sections revealed that PE-PMs induced inflammation in ovarian tissues and impaired oocyte development. TUNEL analysis showed an increased rate of apoptosis in ovarian cells treated with PE-PMs. RT-PCR and Western Blot assays confirmed that exposure to PE-MPs significantly decreased miR-132 expression while increasing CAPN expression at both mRNA and protein levels. The concentration of calcium ions was significantly increased in tissues, leading to CAPN enzyme activity increase. The expression of mitochondrial damage-related genes (bax, AIF, cyt-c, caspase-7, caspase-9, and caspase-3) was higher while the expression of anti-apoptotic genes (bcl-2 and bcl-xl) was lower. Protein levels of bax, AIF, caspase-3, bcl-2 and bcl-xl changed accordingly with the genetic alterations. Additionally, we discovered that PE-MPs can activate the p65 factor through the TRAF6/NF-kB pathway resulting in elevated production of pro-inflammatory factors IL-6, IL-1ß and TNF-a which contribute to ovarian inflammation development. This study investigates the impact of PE-MPs on carp ovarian function and provides insights into miRNAs' role and their target genes.

Microplastics induced inflammation and apoptosis via ferroptosis and the NF-κB pathway in carp.

Microplastics (MPs), a new class of pollutant that threatens aquatic biodiversity, are becoming increasingly prevalent around the world. Fish growth may be severely inhibited by microplastics, resulting in severe mortality. Exposure to microplastics increases the likelihood of intestinal injuries, but the underlying mechanisms remain equivocal. The objective of this study was to investigate the potential toxic mechanisms underlying microplastic-induced intestinal injury in fish and to assist researchers in identifying novel therapeutic targets. In this study, a model of carp exposed to microplastics was established successfully. Histological observation showed that exposure to polyethylene microplastics caused damage to the intestinal mucosal surface and a significant increase in goblet cells, which aggregated on the surface of the mucosa. The mucosal layer was observed to fall off. Lymphocytes in the intestinal wall proliferated and aggregated. TUNEL staining showed that apoptosis occurred in the group exposed to microplastics. The qPCR results showed that the expression of Ferroptosis apoptotic factors COX-2 and ACSL4 was upregulated, while the expression of TFRC, FIH1, SLC7A11, and GPX4 was downregulated. The NF-κB pathway (p-p65, IκBα), inflammatory cytokines (TNF-α, IL-8, IL-6) and apoptosis genes (Bax, Caspase3) were upregulated. Semi-quantitative detection of related proteins by Western blotting was consistent with the gene expression results. In addition, the ELISA assay showed that lipid peroxidation and inflammatory cytokines (TNF-α, IL-1ß, IL-6) were increased in the microplastic exposed group. To conclude, lipid peroxidation induced by microplastics activates the NF-κB pathway and causes ferroptosis, ultimately resulting in intestinal damage and cellular apoptosis.

Zinc deficiency causes oxidative stress, endoplasmic reticulum stress, apoptosis and inflammation in hepatocytes in grass carp.

A lack of the trace element zinc (Zn) in freshwater environments causes slow growth and malnutrition and affects the normal biological functions of organisms. In this study, a Zn deficiency model of grass carp hepatocytes was established with TPEN. Acetylcysteine (NAC) was used as an inhibitor. TPEN was added to L8824 cell culture medium, and LDH, AST, ALT, and AKP activities were enhanced in a Zn-deficient environment, leading to abnormal hepatopancreas function. Fluorescence microscopy showed an increase in ROS levels, and antioxidant enzyme activity assays revealed that SOD, CAT, GSH-PX, and T-AOC activities were decreased, indicating oxidative stress caused by Zn deficiency. The RT‒PCR results showed that the mRNA expression of GRP78, PERK, EIF2α, ATF4, and Chop was increased due to the addition of TPEN. Calcium kits showed increased Ca2+ levels. The RT‒PCR results showed that the mRNA expression levels of Caspase-12, Caspase-9, Caspase-3, and PARP apoptotic were increased due to the addition of TPEN. RT‒PCR and ELISA showed that the expression levels of interleukin-1ß (IL-1ß), interleukin-8 (IL-8), tumour necrosis factor (TNF-α), and inducible nitric oxide synthase (iNOS) were increased. This led to the conclusion that Zn deficiency in the freshwater environment caused inflammation and apoptosis in hepatocytes in grass carp. For the first time, apoptosis caused by endoplasmic reticulum stress in grass carp hepatocytes due to Zn deficiency was studied in the context of Ca2+. The present study provided some insight into the adverse effects of Zn deficiency in freshwater environments on fish.

Selenium deficiency induced inflammation and apoptosis via NF-κB and MAPKs pathways in muscle of common carp (Cyprinus carpio L.).

Selenium (Se), one of the essential trace elements of fish, regulates immune system function and maintains immune homeostasis. Muscle is the important tissue that generate movement and maintain posture. At present, there are few studies on the effects of Se deficiency on carp muscle. In this experiment, carps were fed with dietary with different Se content to successfully establish a Se deficiency model. Low-Se dietary led to the decrease of Se content in muscle. Histological analysis showed that Se deficiency resulted in muscle fiber fragmentation, dissolution, disarrangement and increased myocyte apoptosis. Transcriptome revealed a total of 367 differentially expressed genes (DEGs) were screened, including 213 up-regulated DEGs and 154 down-regulated DEGs. Bioinformatics analysis showed that DEGs were concentrated in oxidation-reduction process, inflammation and apoptosis, and were related to NF-κB and MAPKs pathways. Further exploration of the mechanism showed that Se deficiency led to excessive accumulation of ROS, decreased the activity of antioxidant enzymes, and also resulted in increased expression of the NF-κB and MAPKs pathways. In addition, Se deficiency significantly increased the expressions of TNF-α, IL-1ß and IL-6, and the pro-apoptotic factors BAX, p53, caspase-7 and caspase-3, while decreased the expressions of anti-apoptotic factors Bcl-2 and Bcl-xl. In conclusion, Se deficiency reduced the activities of antioxidant enzymes and led to excessive accumulation of ROS, which caused oxidative stress and affected the immune function of carp, leading to muscle inflammation and apoptosis.

[Effect of up-regulation of Decorin on expression of EGFR, C-Myc and p21 in nude mice with oral squamous cell carcinoma].

PURPOSE: To explore the effect of overexpression of DCN（decorin） gene on the expression of epidermal growth factor receptor (EGFR), cellular-myelocytomatosis viral oncogene (C-Myc) and cyclin dependent kinase inhibitor (p21)in tumor-bearing nude mice with oral squamous cell carcinoma（OSCC）. METHODS: The expression of DCN gene in human oral squamous cell carcinoma(HSC-3) was up-regulated by liposome transfection. Nude mice were used as the carrier of OSCC. H-E staining was used to determine the pathological grade of tumor-bearing tissues in each group. Immunohistochemistry was used to detect the expression of EGFR, C-Myc and p21 protein in tumor-bearing tissues of each group after DCN overexpression. RT-qPCR and Western blot were used to quantitatively detect the expression of EGFR, C-Myc and p21 in tumor-bearing tissues of each group after DCN overexpression, and to determine the effects of DCN overexpression on the expression of EGFR, C-Myc and p21 in tumor-bearing tissues of OSCC nude mice. SPSS 20.0 software package was used for statistical analysis. RESULTS: H-E staining showed that the animal model of OSCC was successfully constructed. The tumor-bearing tissues of nude mice in the plasmid group were significantly lighter than those in the empty vector group and non-transfected group(P＜0.05). IHC results showed that DCN, EGFR, C-Myc and p21 proteins were expressed in the tumor-bearing tissues of nude mice in each group, the expression of DCN,EGFR and C-Myc proteins in the plasmid group was significantly different from the other groups(P＜0.05).There was no significant differece in p21 protein expression in each group(P＞0.05). RT-qPCR and Western blot results showed that DCN, EGFR, C-Myc and p21 were expressed in diffrent degrees in tumor-bearing tissues of nude mice（P＜0.05）. CONCLUSIONS: DCN can inhibit the growth of tumor in OSCC nude mice. In tumor-bearing tissues of nude mice with OSCC, overexpression of DCN can down-regulate the expression of EGFR and C-Myc, and up-regulate the expression of p21.DCN may play an inhibitory role in the occurrence and development of OSCC.

Polystyrene microplastics induce myocardial inflammation and cell death via the TLR4/NF-κB pathway in carp.

Microplastics (MPs) have attracted widespread attention as an emerging environmental pollutant. Especially in aquatic ecosystems, the harm of MPs to aquatic animals has increasingly become a severe environmental problem. In this study, we constructed a carp polystyrene microplastics (PS-MPs) exposure model to explore the damage and mechanism of PS-MPs exposure to carp myocardial tissue. The results of H&E, TUNEL, and AO/EB staining showed that PS-MPs exposure could induce inflammation, apoptosis, and necrosis in carp myocardial tissue and cardiomyocytes. In addition, our study explored the targeting relationship between PS-MPs and TLR4 and found that PS-MPs exposure could significantly increase the expression of TLR4 pathway-related factors. As the concentration of PS-MPs increased, the NF-κB pathway and inflammation-related factors increased dose-dependent. In addition, myocardial injury induced by exposure to PS-MPs was predominantly apoptotic, accompanied by necrosis. In short, our data suggest that PS-MPs cause damage to myocardial tissue via the TLR4\NF-κB pathway. The above findings enrich the theory of toxicological studies on PS-MPs and provide an essential reference for aquaculture.

Polystyrene microplastics induce endoplasmic reticulum stress, apoptosis and inflammation by disrupting the gut microbiota in carp intestines.

Microplastics have been recognized as a widespread new pollutant in nature and have induced an increase in the occurrence of a variety of diseases in carp. An animal model of microplastic ingestion was successfully established in an aqueous environment. The gut microbiota was analysed using a metagenomic approach. The results showed a significant reduction in the relative abundances of Lactococcus garvieae, Bacteroides_paurosaccharolyticus, and Romboutsia_ilealis after PS-MPs treatment. The 16S Silva database was used to predict and analyse the known genes. Intestinal flora disorders related to infectious diseases, cancers, neurodegenerative diseases, endocrine and metabolic diseases, cardiovascular diseases, and other diseases were found. The intake of PS-MPs resulted in damage to carp intestinal tissue and apoptosis of intestinal epithelial cells. The levels of the inflammatory cytokines IL-1ß, IL-6, and TNF-α were significantly increased with the intake of PS-MPs. The gene and protein levels of GRP78, Caspase-3, Caspase-7, Caspase-9, Caspase-12, PERK, IRE1, and ATF6 were further examined in PS group. The occurrence of ERS and apoptosis in carp intestines was confirmed. These results suggest that the accumulation of PS-MPs in the aquatic environment can disturb the carp gut microbiota and induce ERS, apoptosis, and inflammation in the intestinal tissue.

Polystyrene microplastics induced inflammation with activating the TLR2 signal by excessive accumulation of ROS in hepatopancreas of carp (Cyprinus carpio).

Polystyrene microplastics (PS-MPs) affect the immune defense function on carp (Cyprinus carpio). The PS-MPs model of carp was established by feeding with PS-MPs particle size of 8 µm and concentration of 1000 ng/L water. Hepatopancreas function test revealed the activities of AKP, ALT, AST and LDH abnormal increase. PS-MPs induced tissue damage and lead to abnormal hepatopancreas function. The PS-MPs also induced a oxidative stress with the antioxidant enzymes SOD, CAT, GSH-PX, and T-AOC activities decreasing and reactive oxygen species (ROS) excessive accumulation. PS-MPs activated the Toll like receptor-2 (TLR2) signaling pathway. The mRNA and protein expressions of TLR2, Myeloid differentiation primary response 88 (MyD88), tumor necrosis factor receptor-associated factor 6 (TRAF6), NF-κB p65, Tumor necrosis factor (TNF-α), Interleukin-1ß (IL-1ß), Inducible Nitric Oxide Synthase (iNOS), and cycooxygenase 2(COX2) was revealed increased in both hepatopancreas and hepatocytes with the qPCR and Western blotting analysis mode. ELISA showed the expressions of TNF-α, IL-1ß, iNOS, and COX2 inflammatory molecule were increased in both hepatopancreas and hepatocytes. The results showed that PS-MPs caused a serious injure in the hepatopancreas and brought serious effects on the inflammatory response of carp. The present study displayed the harm caused by PS-MPs in freshwater fish, and provided some suggestions and references for toxicological studies of microplastics in freshwater environment.

Polyethylene microplastics trigger cell apoptosis and inflammation via inducing oxidative stress and activation of the NLRP3 inflammasome in carp gills.

Microplastics cause varying degrees of damage to aquatic organisms. Exposure to microplastics contaminated water, the gills are among the first tissues, after the skin, to be affected by microplastics. As an essential immune organ, prolonged stimulation by microplastics disrupts immune function not only in the gills but throughout the body, yet the underlying mechanisms remain elusive. A model of gill injury from exposure to polyethylene (PE) microplastics was developed in this study. H&E staining revealed that polyethylene microplastics caused gill inflammation, vascular remodeling, and mucous cell proliferation. An increase in collagen indicates severe tissue damage. Additional analysis showed that polyethylene microplastics profoundly exacerbated oxidative stress in the gills. TUNEL assay demonstrated cell apoptosis induced by polyethylene microplastic. The mRNA levels were subsequently quantified using RT-PCR. The results showed that polyethylene microplastics increased the expression of the nuclear factor-κB (NF-κB) pathway (NF-κB p65, IKKα, IKKß) and apoptosis biomarkers (p53, caspase-3, caspase-9, and Bax). Nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasomes, which is an influential component of innate immunity, were overactive. What's more, the pro-inflammatory factors (TNF-α, IFN-γ, IL-2, IL-6, IL-8, IL-1ß) that induce immune disorder also increased significantly, while the anti-inflammatory factors (IL-4, IL-10) decreased significantly. These results suggested that oxidative stress acted as an activation signal of apoptosis triggered by the NF-κB pathway and activating the NLRP3 inflammasome to promote inflammatory immune responses. The present study provided a different target for the prevention of toxin-induced gill injury under polyethylene microplastics.

Selenium Deficiency Caused Fibrosis as an Oxidative Stress-induced Inflammatory Injury in the Lungs of Mice.

Selenium (Se) is a vital trace element in the regulation of inflammation and antioxidant reactions in both animals and humans. Se deficiency is rapidly affecting lung function. The present study investigated the molecular mechanism of Se deficiency aggravates reactive oxygen species (ROS)-induced inflammation, leading to fibrosis in lung. Mice fed with different concentrations of Se to establish the model. In the Se-deficient group, the ROS and malondialdehyde (MDA) was increased, and the activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), total antioxidant capacity (T-AOC), and catalase (CAT) reduced. The histopathological observation showed that Se deficiency lead to lung texture damage with varying degrees of degeneration, necrosis, shedding of some alveolar epithelial cells, and inflammatory cell infiltration. Immunohistochemistry showed that the expression of α-smooth muscle actin (α-SMA) increased. The fibrosis index was verified with Sirius red staining. The ELISA and qPCR results showed that the inflammatory cytokines (TNF-α and IL-1ß) and ECM (collagen I, collagen IV, fibronectin, and laminin) were increased with ROS increasing, which was induced by Se deficiency. The results displayed that oxidative stress with Se deficiency led to an increase in tissue inhibitors of metalloproteinase (TIMPs), but a decrease in matrix metalloproteinases (MMPs). All the results indicated that Se deficiency induced excessive ROS accumulation to generate inflammation, which disrupted ECM homeostasis and aggravated fibrosis in the lung.

Selenium Deficiency Leads to Reduced Skeletal Muscle Cell Differentiation by Oxidative Stress in Mice.

Selenium (Se) is one of the essential trace elements in animal organisms with good antioxidant and immune-enhancing abilities. In this study, we investigated the effect and mechanism of Se deficiency on skeletal muscle cell differentiation. A selenium-deficient skeletal muscle model was established. The skeletal muscle tissue and blood Se content were significantly reduced in the Se deficiency group. HE staining showed that the skeletal muscle tissue had a reduced myofiber area and nuclei and an increased myofascicular membrane with Se deficiency. The TUNEL test showed massive apoptosis of skeletal muscle cells in Se deficiency. With Se deficiency, reactive oxygen species (ROS) and malondialdehyde (MDA) increased, and the activities of glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC), superoxide dismutase (SOD), and catalase (CAT) were inhibited. In in vitro experiments, microscopic observations showed that the low-Se group had reduced C2C12 cell fusion and a reduced number of differentiated myotubes. In addition, qPCR results showed that differentiation genes (Myog, Myod, Myh2, Myh3, and Myf5) were significantly reduced in the low Se group. Meanwhile, Western blot analysis showed that the levels of differentiation proteins (Myog, Myod, and Myhc) were significantly reduced in the low-Se group. This finding indicates that Se deficiency reduces the expression of skeletal muscle cell differentiation factors. All the above data suggest that Se deficiency can lead to oxidative stress in skeletal muscle, resulting in a reduction in the differentiation capacity of muscle cells.

Berberine Depresses Inflammation and Adjusts Smooth Muscle to Ameliorate Ulcerative Colitis of Cats by Regulating Gut Microbiota.

Intestinal microbiota dysbiosis is a well established characteristic of ulcerative colitis (UC). Regulating the gut microbiota is an effective UC treatment strategy. Berberine (BBR), an alkaloid extracted from several Chinese herbs, is a common traditional Chinese medicine. To establish the efficacy and mechanism of action of BBR, we constructed a UC model using healthy adult shorthair cats to conduct a systematic study of colonic tissue pathology, inflammatory factor expression, and gut microbiota structure. We investigated the therapeutic capacity of BBR for regulating the gut microbiota and thus work against UC in cats using 16S rRNA genes amplicon sequencing technology. Our results revealed that dextran sulfate sodium (DSS)-induced cat models of UC showed weight loss, diarrhea accompanied by mucous and blood, histological abnormalities, and shortening of the colon, all of which were significantly alleviated by supplementation with BBR. A 16S rRNA gene-based microbiota analysis demonstrated that BBR could significantly benefit gut microbiota. Western blot, quantitative PCR, and enzyme-linked immunosorbent assays (ELISAs) showed that in DSS-induced cat models, the expression of the inflammatory factors was increased, activating the JAK2/STAT3 signaling pathway, and treatment with BBR reversed this effect. The myosin light chain (MLC) phosphorylation in the smooth muscle of the intestines is associated with motility of inflammation-related diarrhea in cats. This study used gut flora analyses to demonstrate the anti-UC effects of BBR and its potential therapeutic mechanisms and offers novel insights into the prevention of inflammatory diseases using natural products. IMPORTANCE Ulcerative colitis (UC) is common in clinics. Intestinal microbiota disorder is correlated with ulcerative colitis. Although there are many studies on ulcerative colitis in rats, there are few studies on colitis in cats. Therefore, this study explored the possibility of the use of BBR as a safe and efficient treatment for colitis in cats. The results demonstrated the therapeutic effects of BBR on UC based on the state of the intestinal flora. The study found BBR supplementation to be effective against dextran sulfate sodium (DSS)-induced colitis, smooth muscle damage, and gut microbiota dysbiosis.

LncRNAs Transcriptome Analysis Revealed Potential Mechanisms of Selenium to Mastitis in Dairy Cows.

The trace element selenium (Se) plays an indispensable role in the growth of humans and animals due to its antioxidant function. Mastitis is one of the most important diseases affecting the dairy industry in the world. In recent years, long non-coding RNAs (lncRNAs) have been implicated in a series of cellular processes and disease development processes. RNA-sequencing technology was used to characterize lncRNA profiles and compared transcriptomic dynamics among the control group, the LPS group, and the Se-treated group to highlight the potential roles and functions of lncRNAs in the mammary epithelial cells of dairy cows. We identified 14 specific lncRNAs related to Se and their predicted target genes. KEGG and GO functional annotation was used to elucidate their biological function and the pathways in which they may be involved. The present study provides novel insights for exploring the molecular markers for the protection of Se against mastitis in dairy cows.

Zinc Deficiency Aggravates Oxidative Stress Leading to Inflammation and Fibrosis in Lung of Mice.

Zinc (Zn) is an essential trace element for the body. Studies have confirmed that Zn deficiency can cause oxidative stress. The purpose of the present study was designed to investigate the effect of Zn on fibrosis in lung of mice and its mechanism. Mice were fed with different Zn levels dietary, then we found that the Zn-deficient diet induced a decrease of Zn level in lung tissue. The results also revealed the alveolar structure hyperemia and an inflammatory exudated in the alveolar cavity. Moreover, immunohistochemical results showed that the expression of α-smooth muscle actin (α-SMA) increased. And the Sirius red staining indicated an increase in collagen with Zn deficiency. Furthermore, oxygen radicals (ROS) levels were significantly increased, and the antioxidants were significantly decreased. Meanwhile, inflammatory factors (TNF-α and IL-1ß) were remarkably increased, and the ELISA results showed that collagen I, III, and IV and fibronectin (FN) were increased. In addition, the expressions of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinase (TIMPs) were detected by qPCR. The results showed that the expression of TIMPs was increased but the expression of MMPs was decreased. The results of the experiment in vitro were consistent with that in vivo. All the results indicated that Zn deficiency aggravated the oxidative stress response of lung tissue to induce inflammation, leading to fibrosis in lung.

Ammonia induces autophagy via circ-IFNLR1/miR-2188-5p/RNF182 axis in tracheas of chickens.

Ammonia (NH3 ), an air pollutant in the living environment, has many toxic effects on various tissues and organs. However, the underlying mechanisms of NH3 -induced tracheal cell autophagy remains poorly understood. In present study, chickens and LMH cells were used as NH3 exposure models to investigate toxic effects. The change of tracheal tissues ultrastructure showed that NH3 exposure induced autolysosomes. The differential expression of 12 circularRNAs (circRNAs) was induced by NH3 exposure using circRNAs transcriptome analysis in broiler tracheas. We further found that circ-IFNLR1 was down-regulated, and miR-2188-5p was up-regulated in tracheal tissues under NH3 exposure. Bioinformatics analysis and dual luciferase reporter system showed that circ-IFNLR1 bound directly to miR-2188-5p and regulated each other, and miR-2188-5p regulated RNF182. Overexpression of miR-2188-5p caused autophagy and its inhibition partially reversed autophagy in LMH cells which were caused by ammonia stimulation or knockdown of circ-IFNLR1. The expressions of three autophagy-related genes (LC3, Beclin 1, and BNIP3) were observably up-regulated. Our results indicated that NH3 exposure caused autophagy through circ-IFNLR1/miR-2188-5p/RNF182. These results provided new insights for the study of ammonia on environmental toxicology on ceRNA and circRNAs in vivo and vitro.