Hepatotoxicity effects of Ageratina adenophora, as indicated by network toxicology combined with metabolomics and transcriptomics.

Ageratina adenophora (A. adenophora), one of the prominent invasive plants in the Asian continent has shown toxicity in animals. However, studies examining the gene expression and metabolic profiles of animals that ingest A. adenophora have not yet been reported in the literature. Therefore, considering the wide distribution of A. adenophora, it is necessary to elucidate the toxic mechanisms of A. adenophora via multiomics approach. In this study, we identified and evaluated the toxic mechanisms of action associated with bioactive compounds in A. adenophora by using network toxicology studies combined with metabolomics and transcriptomics and found that 2-deoxo-2-(acetyloxy)- 9-oxoageraphorone, 10Hß-9-oxo-agerophorone, 10Hα-9-oxo-agerophorone, nerolidol, 9-oxo-10,11-dehydro-agerophorone were the main active toxic compounds in A. adenophora. In addition, using metabolomics approach we identified differential metabolites such as L-pyroglutamic acid, 1-methylhistidine, prostaglandin F2alpha and hydrocortisone from A. adenophora and these metabolites were involved in amino acid metabolism, lipid metabolism and signal conducting media regulation. Based on network toxicological analysis, we observed that, A. adenophora can affect the Ras signaling, Phospholipase D signaling and MAPK signaling pathways by regulating EGFR, PDGFRB, KIT and other targets. From the results of this study we concluded that A. adenophora induces liver inflammatory damage by activating the EGFR expression and Ras/Raf/MEK/ERK signaling pathways as well as affect nutrients metabolism and neuron conduction.

Zinc Oxide Quantum Dots May Provide a Novel Potential Treatment for Antibiotic-Resistant Streptococcus agalactiae in Lama glama.

Streptococcus agalactiae is a significant pathogen that can affect both human beings and animals. The extensive current use of antibiotics has resulted in antibiotic resistance. In our previous research, we found that zinc oxide quantum dots (ZnO QDs) had inhibitory effects on antibiotic-resistant microorganisms. In this study, a strain of Streptococcus agalactiaeWJYT1 with a broad antibiotic-resistant spectrum was isolated and identified from Lama glama at Sichuan Agricultural University Teaching Animal Hospital. The genome for the resistance and virulence genes was analyzed. Additionally, the antibacterial effects and anti-virulence mechanism of ZnO QDs for S. agalactiaeWJYT1 were investigated. The results showed that the genome of S. agalactiaeWJYT1 is 1,943,955 bp, containing 22 resistance genes and 95 virulence genes. ZnO QDs have a good antibacterial effect against S. agalactiaeWJYT1 by reducing bacterial growth and decreasing the expression of virulence genes, including bibA, hylB, sip, and cip, which provides a novel potential treatment for S. agalactiae.

Natural Products as Mite Control Agents in Animals: A Review.

Mites have been a persistent infectious disease affecting both humans and animals since ancient times. In veterinary clinics, the primary approach for treating and managing mite infestations has long been the use of chemical acaricides. However, the widespread use of these chemicals has resulted in significant problems, including drug resistance, drug residues, and environmental pollution, limiting their effectiveness. To address these challenges, researchers have shifted their focus towards natural products that have shown promise both in the laboratory and real-world settings against mite infestations. Natural products have a wide variety of chemical structures and biological activities, including acaricidal properties. This article offers a comprehensive review of the acaricidal capabilities and mechanisms of action of natural products like plant extracts, natural compounds, algae, and microbial metabolites against common animal mites.

Prediction of 5-year overall survival of tongue cancer based machine learning.

OBJECTIVE: We aimed to develop a 5-year overall survival prediction model for patients with oral tongue squamous cell carcinoma based on machine learning methods. SUBJECTS AND METHODS: The data were obtained from electronic medical records of 224 OTSCC patients at the PLA General Hospital. A five-year overall survival prediction model was constructed using logistic regression, Support Vector Machines, Decision Tree, Random Forest, Extreme Gradient Boosting, and Light Gradient Boosting Machine. Model performance was evaluated according to the area under the curve (AUC) of the receiver operating characteristic curve. The output of the optimal model was explained using the Python package (SHapley Additive exPlanations, SHAP). RESULTS: After passing through the grid search and secondary modeling, the Light Gradient Boosting Machine was the best prediction model (AUC = 0.860). As explained by SHapley Additive exPlanations, N-stage, age, systemic inflammation response index, positive lymph nodes, plasma fibrinogen, lymphocyte-to-monocyte ratio, neutrophil percentage, and T-stage could perform a 5-year overall survival prediction for OTSCC. The 5-year survival rate was 42%. CONCLUSION: The Light Gradient Boosting Machine prediction model predicted 5-year overall survival in OTSCC patients, and this predictive tool has potential prognostic implications for patients with OTSCC.

In vitro evaluation of the composition and acaricidal efficacy of Urtica fissa leaf ethyl acetate extract against Sarcoptes scabiei mites.

In veterinary medicine, natural products provide an alternative to chemical agents for mite management. In the present study, the acaricidal efficacy of Urtica fissa leaf ethyl acetate extract against Sarcoptes scabiei mites was examined. The chemical composition of the extract was determined using liquid chromatography-mass spectrometry (LC-MS) analysis. The ethyl acetate extract was found to be extremely toxic to mites at a concentration of 100 mg/ml (m/v), killing all S. scabiei within two hours. The median lethal time (LT50) values for ethyl acetate extract concentrations of 25, 50, and 100 mg/ml against S. scabiei were 1.706, 1.204, and 0.750 h, respectively. The median lethal dosage (LC50) for S. scabiei was 19.14 mg/ml at two hours. The chemical composition of the ethyl acetate extract was evaluated using LC-MS, showing that the major components were schaftoside (8.259%), carnosol (6.736%), prostaglandin A2 (5.94%), 13(S)-HpOTrE (4.624%), nandrolone (4.264%), 1H-indole-3-carboxaldehyde (4.138%), 9-oxoODE (3.206%), and stearidonic acid (2.891%). In conclusion, these findings indicate that Urtica fissa contains promising new acaricidal compounds capable of successfully controlling animal mites.

Comparative study of photoplethysmographic waveforms with application of antihypertensive medication in hypertensive patients.

BACKGROUND: Multiple studies have been published using a pulse oximeter's photoplethysmographic (PPG) capability to detect tissue perfusion. However, the origin of the PPG signal is still debatable. AIM: A comparative study was performed of PPG waveforms in hypertensive patients before and after treatment with antihypertensive medication. The aim of this study was to observe the changes of PPG waveforms before and after lowering blood pressure in hypertensive patients and then to detect the relationship between blood pressure and PPG waveforms. METHODS: The PPG waveforms of 60 patients with hypertension were collected. After administration of the antihypertensive medication nitroglycerin, PPG waveforms were collected again. The changes of the T3 (time3): This phase occurred between Marker 3 and Marker 4 (this phase occurs mid-diastolic) angle, before and after the antihypertensive medication treatment, were compared. The statistical analyses of two related groups were performed using the Paired t-test. RESULTS: The blood perfusion waveforms of hypertensive patients before and after antihypertensive medication administration were differently indicated with the tilt angle T3. The slope angle of the T3 phase waveform increased significantly when the blood pressure dropped to normal (-41.9 ± 16.2° vs. -25.6 ± 21.9°, p < .0001), and the tilt angle of some patients was similar to that of adults with normal blood pressure. CONCLUSION: In patients with hypertension, the tilt angle of the PPG waveform in the T3 phase increased significantly after administration of the antihypertensive medication nitroglycerin. It is worth to conduct deeper research about the relationship between hypertension and the blood perfusion of microcirculation in the diastolic period.

Glycine Nano-Selenium Enhances Immunoglobulin and Cytokine Production in Mice Immunized with H9N2 Avian Influenza Virus Vaccine.

This study was performed to investigate the immune enhancement effect of glycine nano-selenium, a microelement on H9N2 avian influenza virus vaccine (H9N2 AIV vaccine) in mice. Fifty (50) Specific Pathogen Free Kunming mice aged 4−6 weeks (18−20 g Body weight) were randomly divided into five groups: control normal group, which received no immunization + 0.5 mL 0.9% normal saline, positive control group, which received H9N2 AIV vaccine + 0.5 mL 0.9% normal saline, 0.25 mg/kg selenium group, which received H9N2 AIV vaccine + 0.5 mL 0.25 mg/kg selenium solution, 0.5 mg/kg selenium group, which received H9N2 AIV vaccine + 0.5 mL 0.5 mg/kg selenium solution, and 1 mg/kg selenium group, which received H9N2 AIV vaccine + 0.5 mL 1 mg/kg selenium solution. Hematoxylin and eosin staining, enzyme linked immunosorbent assay (ELISA), and quantitative real time polymerase chain reaction (qRT-PCR) methods were used to investigate the pathological changes, immunoglobulin levels, and cytokine gene expressions in this study. The results showed that all tested doses (0.25 mg/kg, 0.5 mg/kg and 1.00 mg/kg) of glycine nano-selenium did not lead to poisoning in mice. In addition, when compared to the positive control group, glycine nano-selenium increased the immunoglobin indexes (IgA, IgG, IgM and AIV-H9 IgG in serum) as well as the mRNA levels of IL-1ß, IL-6 and INF-γ in the liver, lungs, and spleen (p < 0.05). In summary, glycine nano-selenium could enhance the efficacy of avian influenza vaccine.

RNA-binding protein Hfq plays a vital role in cellulose decomposition throughout affecting cellulase gene expression.

OBJECTIVE: To study the function of the RNA-binding protein Hfq in Bacillus subtilis cellulose decomposition. RESULTS: In the medium with sodium carboxymethylcellulose (Na-CMC) as the sole carbon source, the knockout of Hfq resulted in a 38.0% ± 2.1% and 76.6% ± 7.1% decrease in cellulose hydrolysis ability and cellulase activity, respectively. The results of real-time quantitative PCR revealed that several cellulase genes (eglS, bglA, and bglC) were significantly downregulated in the Hfq knockout strain. The isogenic Δhfq complemented strain recovered the cellulose hydrolysis ability, cellulase activity, and expression level of cellulase genes. In addition, the survival of Hfq mutant in stationary phase was significantly affected. CONCLUSION: RNA-binding protein Hfq is involved in the regulation of cellulose hydrolysis ability, cellulase activity, cellulase gene expression, and stationary phase survival.

An Overview: The Toxicity of Ageratina adenophora on Animals and Its Possible Interventions.

Ageratina adenophora is one of the major invasive weeds that causes instability of the ecosystem. Research has reported that A. adenophora produces allelochemicals that inhibit the growth and development of food crops, and also contain some toxic compounds that cause toxicity to animals that consume it. Over the past decades, studies on the identification of major toxic compounds of A. adenophora and their toxic molecular mechanisms have been reported. In addition, weed control interventions, such as herbicides application, was employed to reduce the spread of A. adenophora. However, the development of therapeutic and prophylactic measures to treat the various A. adenophora-induced toxicities, such as hepatotoxicity, splenotoxicity and other related disorders, have not been established to date. The main toxic pathogenesis of A. adenophora is oxidative stress and inflammation. However, numerous studies have verified that some extracts and secondary metabolites isolated from A. adenophora possess anti-oxidation and anti-inflammation activities, which implies that these extracts can relieve toxicity and aid in the development of drug or feed supplements to treat poisoning-related disorders caused by A. adenophora. Furthermore, beneficial bacteria isolated from rumen microbes and A. adenophora can degrade major toxic compounds in A. adenophora so as to be developed into microbial feed additives to help ameliorate toxicity mediated by A. adenophora. This review presents an overview of the toxic mechanisms of A. adenophora, provides possible therapeutic strategies that are available to mitigate the toxicity of A. adenophora and introduces relevant information on identifying novel prophylactic and therapeutic measures against A. adenophora-induced toxicity.

Compensatory combination of romidepsin with gemcitabine and cisplatin to effectively and safely control urothelial carcinoma.

BACKGROUND: Human urothelial carcinoma (UC) has a high tendency to recur and progress to life-threatening advanced diseases. Advanced therapeutic regimens are needed to control UC development and recurrence. METHODS: We pursued in vitro and in vivo studies to understand the ability of a triple combination of gemcitabine, romidepsin, and cisplatin (Gem+Rom+Cis) to modulate signalling pathways, cell death, drug resistance, and tumour development. RESULTS: Our studies verified the ability of Gem+Rom+Cis to synergistically induce apoptotic cell death and reduce drug resistance in various UC cells. The ERK pathway and reactive oxygen species (ROS) played essential roles in mediating Gem+Rom+Cis-induced caspase activation, DNA oxidation and damage, glutathione reduction, and unfolded protein response. Gem+Rom+Cis preferentially induced death and reduced drug resistance in oncogenic H-Ras-expressing UC vs. counterpart cells that was associated with transcriptomic profiles related to ROS, cell death, and drug resistance. Our studies also verified the efficacy and safety of the Gem plus Rom+Cis regimen in controlling UC cell-derived xenograft tumour development and resistance. CONCLUSIONS: More than 80% of UCs are associated with aberrant Ras-ERK pathway. Thus the compensatory combination of Rom with Gem and Cis should be seriously considered as an advanced regimen for treating advanced UCs, especially Ras-ERK-activated UCs.

Relationships between placental adiponectin, leptin, visfatin and resistin and birthweight in cattle.

Adipokines can affect intrauterine development while calf birthweight (CBW) is a breeding standard of calves, which reflects the status of fetal intrauterine development. To explore the correlation between placental adipokines and CBW, 54 healthy Chinese Holstein cows were used in the present study. The cows were grouped according to the CBW of their calves. Placentas were collected immediately after delivery and enzyme-linked immunosorbent assay and reverse transcription-polymerase chain reaction were used to detect the placental expression levels of adiponectin, leptin, visfatin and resistin. Our results show that the mRNA transcription and blood placental content of adiponectin, leptin, visfatin and resistin increased with increasing CBW. The analysis showed that the mRNA transcription levels of placental adiponectin, leptin and resistin were positively correlated with CBW. The mRNA and protein expression levels of adiponectin, leptin and visfatin between the three groups were significantly correlated. Placental resistin mRNA levels correlated positively with adiponectin mRNA, but not leptin or visfatin. The protein expression levels of resistin were significantly positively correlated with those of adiponectin, leptin and visfatin. These results suggest that placental adipokines play important roles in regulating calf intrauterine growth.

Resistin up-regulates LPL expression through the PPARγ-dependent PI3K/AKT signaling pathway impacting lipid accumulation in RAW264.7 macrophages.

Resistin is a cysteine-rich cytokine, which has been indicated as a mediator of insulin resistance and inflammation. Previous studies demonstrated that lipoprotein lipase (LPL) was an important enzyme that could mediate lipid accumulation in macrophages. Additionally, the intracellular molecules phosphatidylinositol 3-kinase (PI3K)/serine-threonine protein kinase (AKT)/peroxisome proliferator-activated receptor (PPARγ) were supposed to be involved in the lipid accumulation process in cells. However, it remains unclear whether resistin was correlated with the dysregulation of lipid metabolism in macrophages. The present study investigated that resistin could up-regulate the expression of LPL and increase the contents of intracellular triglyceride (TG) and total cholesterol (TC) in RAW264.7 macrophages. In addition, intracellular molecules PI3K, AKT and PPARγ were significantly up-regulated and activated in resitin-stimulated RAW264.7 macrophages (P < 0.05). In contrast, the effects of resistin on RAW264.7 macrophages could be abrogated by specific inhibitors for LPL (LPL-siRNA) and PI3K/AKT signaling pathway (LY294002). All together, this study demonstrated that resistin could up-regulate the expression of LPL and induce lipid accumulation in RAW264.7 macrophages. More importantly, the PPARγ-dependent PI3K/AKT signaling pathway was relevant to the lipid accumulation process in resistin-stimulated macrophages.

Occurrence and Genetic Characteristics of Cryptosporidium hominis and Cryptosporidium andersoni in Horses from Southwestern China.

A total of 333 fecal specimens from horses in southwestern China were genotyped based on analysis of the small subunit rRNA (SSU rRNA) gene. Cryptosporidium hominis and Cryptosporidium andersoni were identified in 2 and 4 stool specimens, respectively. The identification of C. hominis was confirmed by sequence analysis of the 70-kDa heat shock protein (HSP70) and oocyst wall protein (COWP) genes. Subtyping analysis of the 60-kDa glycoprotein (GP60) gene sequence of C. hominis revealed a new rare subtype Id, named IdA15; only three Id isolates have been reported in humans to date. Multilocus sequence typing (MLST) analysis indicated that the C. andersoni subtype was A6, A5, A2, and A1 at the four minisatellite loci (MS1, MS2, MS3, and MS16, respectively). This is the first report to identify the presence of C. andersoni and C. hominis in horses in southwestern China and the first to identify a rare zoonotic subtype Id of C. hominis in horses. These findings suggest that infected horses may act as potential reservoirs of Cryptosporidium to transmit infections to humans.

Swainsonine exposure induces impairment of host immune response in pregnant BALB/c mice.

BACKGROUND: Swainsonine can cause serious disorders in reproduction of livestock, affecting both corpora lutea and reproductive hormone. The purpose of this study was to investigate the mechanisms of swainsonine about the immunotoxic effects on pregnant mice in vivo. RESULTS: The peripheral Th1/Th2 was detected by Ionomycin and phorbol myristate acetate (PMA)-stimulating peripheral blood mononuclear cells (PBMC) of phase pregnant mice. Relevant cytokines in serum was evaluated after exposed to different dose of swainsonine. Gene expression of IL-1ß, IFN-γ, TNF-α, IL-4 and IL-10 in PBMC was assessed by real-time PCR. Swainsonine caused vacuolization phenomenon of lutein cells and a dose-effect relationship. The IL-1ß, IFN-γ and TNF-α were promoted, but IL-4 and IL-10 were suppressed in serum. Swainsonine significantly increased IL-1ß, IFN-γ and TNF-α nuclear translocation and decreased IL-4 and IL-10. Swainsonine resulted in a significant shift of peripheral Th1/Th2 paradigm to Th1. CONCLUSIONS: Our data demonstrate that the immunomodulatory of swainsonine disturbed the regular immunologic state of the pregnant mice. This may increase the risk of abortion and probably resulted in serious disorders in reproduction of livestock.

Clinical efficacy of 9-oxo-10, 11-dehydroageraphorone extracted from Eupatorium adenophorum against Psoroptes cuniculi in rabbits.

BACKGROUND: Animal acariasis is one of the important veterinary skin diseases. Chemical drugs have been widely used to treat and control this kind of disease. But many chemicals control could increase resistance in target species, toxicity and environmental hazards. We found that the 9-oxo-10, 11-dehydroageraphorone (euptox A) extracted from E. adenophorum has strong toxicity against P. cuniculi in vitro, but the in vivo acaricidal actions of euptox A have yet to be investigated. RESULTS: A 14-day experiment was performed using rabbits that were naturally infested with P. cuniculi on a farm. Rabbits were randomly divided into five groups; animals in groups A, B and C were treated in each ear topically with 4.0 ml of 2.0 and 1.0 g/L (w/v) euptox A, respectively. Animals in groups D and E were treated with ivermectin (by injection; positive controls) and glycerol with water only (by embrocation; negative controls), respectively. Each rabbit was treated twice with separate treatments on days 0 and 7. Rabbits were observed daily and detailed examinations were performed on days 0, 7 and 14, to inspect the presence or absence of mites and scabs/crusts. Seven days after the initial treatment, the mean clinical scores (presence of scabs/crusts) decreased from 3.48, 3.37, 3.43 and 3.45 to 0.37, 0.42, 0.78 and 0.38 in the ears of animals in groups A, B , C and D, respectively, which were similar to the observations recorded in the positive control rabbits. However, the clinical score for negative control rabbits did not increase significantly (P > 0.05) during the experiment, and this changed from 3.32 to 3.37 in the ears, and there were no significant differences in clinical efficacy between left and right ears. After two treatments (0 and 7 d), the rabbits in groups A, B, C and D had recovered completely 14 days after the last treatment and no recurrences of infection were observed. CONCLUSIONS: These results indicate that euptox A was potent compounds for the effective control of animal P. cuniculi in vivo.

Acaricidal activity of 9-oxo-10,11-dehydroageraphorone extracted from Eupatorium adenophorum in vitro.

The acaricidal activity of the 9-oxo-10,11-dehydroageraphorone (euptox A), a cadenine sesquiterpene from Eupatorium adenophorum (E. adenophorum) against Sarcoptes scabiei and Psoroptes cuniculi was tested in vitro. A complementary log-log (CLL) model was used to analyze the data of the toxicity tests in vitro. The results showed euptox A had strong toxicity against mites, killing all S. scabiei at 3 and 4 mg/ml (m/v) concentration, while 4 mg/ml euptox A was also found to kill all P. cuniculi within a 4 h period. Similarly, 2, 3 and 4 mg/ml concentration of euptox A had strong toxicity against S. scabiei, with median lethal time (LT50) values at 0.687, 0.526, 0.326 h, respectively. 3 mg/ml and 4 mg/ml showed strong acaricidal action against P. cuniculi; the LT50 values were 0.693 and 0.493 h, respectively. The median lethal concentration (LC50) values were 1.068 mg/ml for Scabies mite and 0.902 mg/ml for P. cuniculi in 2 h. The results indicate that euptox A has strong acaricidal activity and may exploit as novel drugs for the effective control of animal acariasis.

Multilocus genotype and subtype analysis of Cryptosporidium andersoni derived from a Bactrian camel (Camelus bactrianus) in China.

Fecal specimens from two Bactrian camels were collected in the Ya'an city zoo of China and were examined for Cryptosporidium by centrifugal flotation. One specimen was found to be parasitized by Cryptosporidium via microscopy, and the oocysts were measured to have an average size of 7.03 × 5.50 µm (n > 50). The isolate was genotyped by polymerase chain reaction (PCR) amplification and DNA sequence analysis of the partial 18S rRNA, COWP, and A135 genes, and was confirmed to be Cryptosporidium andersoni with minor nucleotide differences. Multilocus sequence typing (MLST) analysis indicated that the subtype of the camel-derived C. andersoni isolate was A4, A4, A4, and A1 at the four minisatellite loci (MS1, MS2, MS3, and MS16, respectively). Therefore, this isolate belongs to the most common MLST subtype reported in cattle in China and is distinct from two other known camel C. andersoni MLST subtypes (A6, A4, A2, A1 and A6, A5, A2, A1). Animal transmission experiments demonstrated that the C. andersoni isolate was not infectious to immunosuppressed or immunocompetent Kun-ming mice, Sprague-Dawley rats, and hamsters but was biologically similar to most bovine C. andersoni isolates characterized so far. Therefore, transmission of this camel-derived C. andersoni isolate is very likely to occur between camels and bovine.

Photoplethysmography for Assessing Microcirculation in Hypertensive Patients After Taking Antihypertensive Drugs: A Review.

High blood pressure (BP) is a common disease and is associated with many chronic diseases. Measuring BP is essential for the treatment and management of many diseases, and therefore there is a growing need for a non-invasive, sleeveless and continuous BP monitoring device. With the development of technology, pulse waveform analysis using photoplethysmography (PPG) has become more feasible for evaluating BP. This study aimed to evaluate the changes of vascular elasticity and blood volume over time by using the characteristic parameters extracted by PPG. We reviewed the latest progress and literature on the observation of capillary network characteristics in hypertensive and non-hypertensive patients by PPG, the influence of different drugs on microcirculation characteristics in hypertensive patients with PPG, and further explored the key relationship between microcirculation and hypertension. We found that the PPG waveform produced by the fingertips of hypertensive patients is very different from that of healthy people, and the PPG waveform changes significantly during diastolic period after antihypertensive treatment. With the rapid development of medical technology, people can get more intuitive microcirculation image data, which provides beneficial help for the comprehensive understanding of hypertension.

Ageratina adenophora damages the rumen epithelium via inducing the expression of inflammatory factors in goats.

The aim of this experiment was to investigate the effects of Ageratina adenophora on the expression of epithelium tight junction proteins and inflammatory factors in the rumen of goats. Twelve goats were randomly divided into three groups. The first group was the blank control group (n = 3, C) which was fed normal diet. The second group was fistulas control group (n = 3, RFC), which was fitted with rumen fistulas, and fed normal diet. The third group was the A. adenophora test group (n = 6, AA), which was fitted with rumen fistulas and fed a mixture of 60% of normal diet and 40% of A. adenophora grass powder. The feeding experiment lasted for 90 d, after which all goats were sacrificed and samples were collected from the rumen dorsal sac and ventral sac. The relative expression of mRNA of inflammatory factors in the rumen epithelium (tumor necrosis factor alpha [TNF-α], interferon gamma [IFN-γ], interleukin 1 beta [IL-1ß], IL-2, IL-4, IL-6, and IL-10) and tight junction protein genes (occludin, claudin-1, and ZO-1) was measured by quantitative real-time fluorescence PCR. Expression of tight junction proteins in the rumen epithelium was measured by Western blot. A correlation was established between the expression of inflammatory factors and tight junction protein genes using Graph Pad Prism. The results showed that A. adenophora caused a significant increase in the mRNA expression levels of TNF-α, IFN-γ, IL-1ß, IL-2, IL-6, and IL-10 in the rumen epithelial (P < 0.05 or P < 0.01). The expression of tight junction proteins at both gene and protein levels was significantly decreased (P < 0.05 or P < 0.01). Furthermore, the correlation analysis revealed that the changes in tight junction protein expression in the test group were closely related to the upregulation of the expression of inflammatory factors TNF-α and IFN-γ in rumen epithelial cells. In conclusion, the expression of inflammatory factors was increased and the expression of tight junction proteins was decreased in goats after feeding on A. adenophora, which caused some damage to the rumen epithelium.

The article aims to investigate the toxic effects of Ageratina adenophora, an invasive plant on the integrity of the rumen epithelium by measuring the changes in the expression of inflammatory factors and tight junction proteins after the consumption of A. adenophora in goats. The results showed that A. adenophora causes damage to the rumen epithelium by increasing the expression of pro-inflammatory markers like TNF-α and IFN-γ and reducing the expression of tight junction proteins such as occludin and claudin-1 in goats.

Study on the chronic inflammatory injury caused by Ageratina adenophora on goat liver using metabolomics.

Ageratina adenophora (A. adenophora) is an invasive plant that is harmful to animals. The plants toxic effects on the liver have been studied in detail, however, the inflammation aspects of the hepatotoxicity are rarely discussed in literature. Therefore, in this study, we investigated the level of inflammation and the associated changes in liver metabolism caused by A. adenophora ingestion. Goat were fed with A. adenophora powder which accounts for 40% of the forage for 90 d. After the feeding period, the liver tissues were collected and the level of inflammation was detected using H & E staining and the changes in metabolites by LC-MS/MS. The results indicated that A. adenophora changes the liver metabolites, The test group shown 153 different metabolites in liver of which 71 were upregulated and 82 down regulated. We also found two differential metabolic pathways: neuroactive ligand-receptor interaction and pyrimidine metabolism. The changes in the pathway suggested an association with inflammation and with pathological processes such as oxidative stress and apoptosis. In addition, we observed an increase in the levels of serum liver function indexes (AST and ALT), indicating the liver injury. Furthermore, inflammatory cell infiltration and cell degeneration were observed in histopathological sections. In conclusion, this study reveals that A. adenophora causes chronic inflammation and upregulate metabolites related to inflammation in the liver. The study complements the research content of A. adenophora hepatotoxicity and provides a basis for further research by analyzing changes in the liver metabolites.