The mechanism and experimental verification of Ixeris sonchifolia promoting apoptosis of hepatocellular carcinoma based on network pharmacology: Ixeris sonchifolia Induces Hepatocellular Carcinoma Apoptosis via the PI3K/AKT Pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Ixeris sonchifolia alias Kudiezi, it was named Ixeris sonchifolia (Bunge) Hance, a synonym for Crepidiastrum sonchifolium (Bunge) Pak & Kawano in the https://www.iplant.cn/. And it was first published in J. Linn. Soc., Bot. 13: 108 (1873), which was named Ixeris sonchifolia (Maxim.) Hance in the MPNS (http://mpns.kew.org). As a widely distributed medicinal and edible wild plant, it possesses unique bitter-cold characteristics and constituents with various pharmacological activities. Its main antitumor substances, same as artemisinin and paclitaxel, are classified as terpenoids and have become research foci in recent years. However, its specific biological activity and role in antitumor treatment remain largely unclear. AIM OF THE STUDY: This study aimed to elucidate the molecular targets and potential mechanisms of hepatocellular carcinoma apoptosis induced by Ixeris sonchifolia. MATERIALS AND METHODS: We used network pharmacology methods to analyze and screen the active ingredients and possible underlying mechanisms of Ixeris sonchifolia in treating liver cancer and employed integrative time- and dose-dependent toxicity, transcriptomics, and molecular biology approaches to comprehensively verify the function of Ixeris sonchifolia extract (IsE) in human hepatoblastoma cell (HepG2) apoptosis and its potential mechanism. RESULTS: A total of 169 common targets were screened by network pharmacology, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that IsE inhibited HepG2 cell activity in a time- and dose-dependent manner. Western blot analysis confirmed that IsE promoted HepG2 cell apoptosis by inhibiting the PI3K/AKT signaling pathway and that the PI3K/AKT inhibitor LY294002 also substantially enhanced IsE-induced apoptosis. The PI3K/AKT signaling pathway exhibited significant differences compared to that in the control group. CONCLUSION: Combining network pharmacology with experimental verification, IsE inhibited mitochondrial function and the PI3K/AKT pathway while inducing hepatoma cell apoptosis. IsE may have promising potential for liver cancer treatment and chemoprevention.

Three new phenolic glycosides and a new lignan glycoside from Gaultheria leucocarpa var. yunnanensis.

Three new phenolic glycosides (1-3) and a new lignan glycoside (4), together with five known compounds (5-9) were isolated from the ethanol extract of the aerial part of Gaultheria leucocarpa var. yunnanensis (Franch.) T.Z.Hsu & R.C.Fang. Their structures were determined on the basis of spectroscopic techniques, experimental and calculated ECD spectra, acid hydrolysis, and enzymatic hydrolysis experiments. All the isolates were evaluated for their anti-inflammatory and antioxidant activities. Compounds 7 and 8 exhibited inhibitory effects against the LPS-induced production of NO with IC50 of 63.71 and 10.66 µM, respectively, compared to L-NMMA having an IC50 of 6.95 µM. Besides, compound 7 also represented significant DPPH radical scavenging activity with EC50 of 18.75 µM, comparable with vitamin C (EC50 = 15.77 µM).

Pharmacokinetics, anti-rheumatoid arthritis activity, and active ingredient contents of Eucommia ulmoides Oliv.

Eucommia ulmoides Oliv. is a deciduous tree which contains various chemical ingredients. The main objective was to document the active chemical ingredients of Eucommia ulmoides Oliv. and their metabolic profiles in vivo, with a view to providing an experimental and theoretical basis for clarifying the mechanisms underlying the pharmacological activity of Eucommia ulmoides Oliv. against rheumatoid arthritis. Eight main active constituents of Eucommia ulmoides Oliv. bark (pinoresinol glucopyranoside, aucubin, geniposidic acid, geniposide, genipin, chlorogenic acid, quercetin and betulinic acid) were quantified using high-performance liquid chromatography (HPLC). This paper additionally identified and characterized prototype metabolites via ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) combined with the Human Metabolome Database (HMDB) and literature comparisons. Ultra pressure liquid chromatography-mass spectrometry/ mass spectrometry (UPLC-MS/MS) was subsequently employed to quantify these components in blood over time and evaluate their pharmacokinetic characteristics. The anti-rheumatoid arthritis effects of genipin, pinoresinol glucopyranoside and their combinations were assessed using in vitro cellular assays. We identified and characterized a total of 53 ingredients from Eucommia ulmoides Oliv. bark and plasma samples, among which 20 were confirmed as prototype metabolites. Meanwhile, this paper derived and analyzed the metabolic cleavage pathway of 8 index ingredients. Six of these compounds displayed rapid entry into blood, with high plasma exposure and fast elimination rates. Data from the in vitro cellular assay showed that aucubin, pinoresinol glucopyranoside, genipin, and combinations of these compounds effectively inhibit MH7A cell proliferation, reduce NO release, and decrease inflammatory factor levels.

The Effects of Cinobufagin on Hepatocellular Carcinoma Cells Enhanced by MRT68921, an Autophagy Inhibitor.

Cinobufagin, a cardiotonic steroid derived from toad venom extracts, exhibits significant anticancer properties by inhibiting Na[Formula: see text]/K[Formula: see text]-ATPase in cancer cells. It is frequently used in clinical settings to treat advanced-stage cancer patients, improving their quality of life and survival time. However, its long-term use can result in multidrug resistance to other chemotherapy drugs, and the exact mechanism underlying this effect remains unknown. Therefore, this study explores the molecular mechanism underlying the anticancer effects of cinobufagin in hepatocellular carcinomas (HCCs), specifically in HepG2 and Huh-7 cells. As determined using transcriptome analysis, cinobufagin-triggered protective autophagy suppressed cell apoptosis in liver cancer HepG2 and Huh-7 cells by inhibiting the phosphoinositide-3-Kinase (PI3K)-AKT serine/threonine kinase (AKT)-mammalian target of rapamycin (mTOR) pathway. Cinobufagin-inhibited cell proliferation, induced apoptosis, and generated cell autophagy by upregulating the expression of MAP1 light chain 3 protein II, Beclin1, and autophagy-related protein 12-5. In addition, the autophagy inhibitor MRT68921 improved the antiproliferative and proapoptotic effects of cinobufagin in the studied cell lines. Overall, this study suggests that combining cinobufagin with an autophagy inhibitor can effectively treat HCC, providing a potential strategy for cancer therapy.

An evaluation of the qualitative superiority of the Mongolian medicinal herb hurdan-tsagaan (Platycodi Radix) from five different geographic origins based on anti-inflammatory effects.

ETHNOPHARMACOLOGICAL RELEVANCE: The contents and types of the active compounds in medicinal herbs depend greatly on their extraction methods, sources of origin and the modes of cultivation. Platycodon grandiflorus (Jacq.) A.DC. is an ethnic medicinal herb widely cultivated in China, and its dried root, Platycodi Radix (PR), is an important ingredient in herbal formulae for attenuating lung issues in Mongolian medical practice. However, research evaluating the superiority of PR based on harvesting regions is relatively limited. AIM: This study aimed to evaluate the qualitative superiority of PR from different regions based on anti-inflammatory effect. MATERIALS AND METHODS: A total of three commercial PR samples were obtained from Anguo, Bozhou and Shangluo, and two wild samples were obtained from Chifeng and Hinggan. PR extract (PRE) was prepared by water distillation, and platycodin D content in the extract was examined by HPLC-UVD. An optimal dose of PRE was administered to BALB/c mice with S. pneumoniae pneumonia, and IL-10 and TNF-α levels in lung tissue were examined by ELISA. HepG2 cells were treated with PRE, and an analysis of differentially expressed gene and functional enrichment was performed using an HTS2 assay. RESULTS: The contents of moisture, total ash, crude extract and platycodin D in the raw roots met the quality control requirements outlined in the Chinese Pharmacopoeia (2020 edition). The platycodin D content in the aqueous extract of the roots in descending order was 24.16% in PRE_Shangluo, 22.91% in PRE_Hinggan, 21.41% in PRE_Bozhou, 17.8% in PRE_Chifeng and 15.92% in PRE_Anguo. Furthermore, administration of PREs at an optimal dose of 2.0 g/kg resulted in some anti-inflammatory effect in mice with Streptococcus pneumoniae pneumonia, among which PRE_Shangluo administration exhibited a more obvious anti-inflammatory impact as shown by a significant decrease in the plasma white cell count (p < 0.05) and IL-10 level elevation and TNF-α reduction in lung tissue (p < 0.05) after treatment. In HepG2 cells treated with 100 µg/ml of each PRE, PRE_Hinggan and PRE_Shangluo resulted in significant differential expression of genes such as nuclear factor kappa B subunit 1 (NFKB1) and significant enrichment of pathways involved in the immune system, such as PI3K-Akt, MAPK and NF-kappa B signaling pathways. CONCLUSIONS: In this study, based on the anti-inflammatory effect, the quality of PR of Shangluo origin was superior to that of PR from the other four regions.

Organic Selenium Alleviates Ammonia-Mediated Abnormal Autophagy by Regulating Inflammatory Pathways and the Keap1/Nrf2 Axis in the Hypothalamus of Finishing Pigs.

Ammonia is a significant pollutant in the livestock houses and the atmospheric environment, and excessive ammonia would harm the health of livestock and breeders. Previous studies have shown that ammonia exposure could damage the tissue structure of the nervous system, but the molecular mechanism of ammonia-induced hypothalamus damage was still unclear. The purpose of this study was to determine the role of excessive ammonia in abnormal autophagy of pig hypothalamus and whether selenomethionine would have a mitigating effect on ammonia toxicity. Twenty-four 18-week pigs were randomly divided into four groups: the control group (C group), the selenium group (Se group), the ammonia + selenium group (A + Se group), and the ammonia group (A group). In our study, the expression levels of NF-κB, IL-1ß, iNOS, TNF-α, IKK-α, p-IKK-α, Nrf2, ATG5, ATG 10, ATG 12, LC3 I/II, HSP60, HSP70, and HSP90 were increased after ammonia exposure; meanwhile, IFN-γ, IKB-α, p-IKB-α, Keap1, P62, mTOR, AKT, p-AKT, PI3K, SQSTM, and Beclin1 showed decreasing trends. The results indicated that excessive ammonia inhalation inhibited the AKT/mTOR pathway to acclerated autophagy through oxidative stress-mediated inflammation in the porcine hypothalamus. L-selenomethionine could alleviate hypothalamus injury induced by ammonia exposure.

Selenium Mitigates Ammonia-Induced Neurotoxicity by Suppressing Apoptosis, Immune Imbalance, and Gut Microbiota-Driven Metabolic Disturbance in Fattening Pigs.

Ammonia could be regarded as one detrimental pollutant with an acrid smell in livestock sheds. So far, the pig breeding industry became the main source of atmospheric ammonia. Previous literature demonstrated that excessive ammonia inhalation might cause a series of physiological damage to multiple organs. Unfortunately, the toxicity mechanisms of gaseous ammonia to the porcine nervous system need further research to elucidate. Selenium (Se) involves in many essential physiological processes and has a mitigative effect on the exogenous toxicant. There were scant references that corroborated whether organic Se could intervene in the underlying toxicity of ammonia to the hypothalamus. In the present study, multi-omics tools, ethology, and molecular biological techniques were performed to clarify the detailed mechanisms of relaxation effects of L-selenomethionine on ammonia poisoning. Our results showed that ammonia inhalation caused the clinical symptoms and the increment of positive apoptosis rate in the hypothalamus with the dysfunction of mitochondrial dynamics factors, while obvious mitochondria structure defects were observed. In parallel, the inflammation medium levels and gut microbes-driven metabolism function were altered to mediate the neurotoxicity in fattening pigs through the initiation of inflammation development. Interestingly, L-selenomethionine could attenuate ammonia toxicity by activating the PI3K/Akt/PPAR-γ pathway to inhibit the mitochondria-mediated apoptosis process, blocking the abnormal immune response and the accumulation of reactive oxygen species in the nucleus. Meanwhile, Se could enhance the production performance of fattening sows. Taken together, our study verified the novel hypothesis for the toxicity identification of aerial ammonia and provided a therapeutic strategy for the treatment of occupational poisoning.

Selenium Alleviates Ammonia-Induced Splenic Cell Apoptosis and Inflammation by Regulating the Interleukin Family/Death Receptor Axis and Nrf2 Signaling Pathway.

Ammonia (NH3) is a harmful gas in livestock houses. So far, many researchers have demonstrated that NH3 is detrimental to animal and human organs. Selenium (Se) is one of the essential trace elements in the body and has a good antioxidant effect. However, there was little conclusive evidence that Se alleviated NH3 poisoning. To investigate the toxic mechanism of NH3 on pig spleen and the antagonistic effect of L-selenomethionine, a porcine NH3-poisoning model and an L-selenomethionine intervention model were established in this study. Our results showed that NH3 exposure increased the apoptosis rate, while L-selenomethionine supplementation alleviated the process of excessive apoptosis. Immunofluorescence staining, real-time quantitative polymerase chain reaction (qRT-PCR), and western blot results confirmed that exposure to NH3 changed the expression levels of interleukin family factors, apoptosis, death receptor, and oxidative stress factors. Our study further confirmed that excessive NH3 induced inflammatory response and mediated necroptosis leading to cell apoptosis by activating the Nrf2 signaling pathway. Excessive NH3 could mediate spleen injury through oxidative stress-induced mitochondrial dynamics disorder. L-Selenomethionine could alleviate inflammation and abnormal apoptosis by inhibiting the IL-17/TNF-α/FADD axis. Our study would pave the way for comparative medicine and environmental toxicology.

Ameliorative effects of dietary selenium against cadmium toxicity on production performance and egg quality in laying hens.

In order to reveal the influences of supplemented dietary selenium (Se) on the suppressive effect of cadmium (Cd) toxicity on performance and egg properties of laying hens, the effects of co-treatment Se and Cd on the performance, egg quality, levels of amino acids and the antioxidant capacity of egg and serum were investigated. A total of 128 31-week-old laying hens were randomly distributed in four treatments, which were fed with the basic diet (0.2 mg/kg Se and 0.08 mg/kg Cd), and the basic diet with Se (1.1 mg/kg Se and 0.08 mg/kg Cd), Cd (0.2 mg/kg Se and 92.1 mg/kg Cd) and Se+Cd for 13 weeks, respectively. Hens supplemented with Cd led to an impairment on production performance and egg quality with decreased egg production (EP), egg mass (EM), feed intake (FI), eggshell color, eggshell thickness, yolk color, albumen height and haugh unit and increased the feed conversion ratio (FCR) (p < 0.05). Cd treatment decreased the contents of cysteine (Cys), histidine (His), lithium (Li), aluminum (Al), chromium (Cr), manganese (Mn), nickel (Ni), zinc (Zn), arsenic (As), Se, strontium (Sr), stannum (Sn), mercury (Hg) and thallium (Tl) and increased the contents of isoleucine (Ile) and Cd (p < 0.05). Cd destroyed the egg yolk and serum redox states with the increased concentration of malondialdehyde (MDA) and the decreased activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) (p < 0.05). The expression levels of ovarian apoptotic genes (protein 53, Caspase9, Cytochrome c and Bcl-2 associated X protein) increased, and B-cell lymphoma 2 (Bcl-2) expression decreased in the Cd group (p < 0.05). Feeding Se significantly alleviated Cd-induced toxicity on performance and egg quality. Se+Cd treatment restored the balance between oxidation and antioxidant systems and modulated the elements' homeostasis and alleviated the changes in apoptotic-related genes expression levels. Se could alleviate the Cd toxicity to laying hens and their eggs but could not counteract all negative effects of Cd.

Intestinal barrier dysfunction induced by ammonia exposure in pigs in vivo and in vitro: The protective role of L-selenomethionine.

Ammonia has been reported to have a variety of toxicity to aquatic animals, farm animals and humans. However, its potential toxicity on the intestines remains unknown. L-selenomethionine is one of the important organic selenium sources. However, the mitigating effect of L-selenomethionine on ammonia exposure toxicity is still lacking. Therefore, in this study, the mechanism of toxic action of ammonia on intestinal tract and the detoxification effect of L-selenomethionine were examined. We evaluated the intestinal toxicity of ammonia and the alleviating effect of L-selenomethionine in an in vivo model, and then verified it in vitro model by a variety of cutting-edge experimental techniques. Our results showed that ammonia exposure causes oxidative stress, necroptosis, Th1/Th2 imbalance and inflammation in the intestinal tissue and the intestinal cells, and L-selenomethionine had a significant mitigation effect on the changes of these indexes induced by ammonia. In conclusion, ammonia exposure caused oxidative stress and Th1/Th2 imbalance in the porcine small intestine and IPEC-J2 cells, and that excessive ROS accumulation-mediated necroptosis targeted inflammatory responses, resulting in the destruction of tight connections of intestinal cells, thereby causing intestinal barrier dysfunction. L-selenomethionine could effectively reduce the intestinal injury caused by ammonia exposure and antagonize the toxic effect of ammonia.

Roots of Astragalus propinquus Schischkin Regulate Transmembrane Iron Transport and Ferroptosis to Improve Cerebral Ischemia-Reperfusion Injury.

Background: The dried roots of the Astragalus propinquus Schischkin (RAP) plant, as a traditional Chinese medicine, has been widely used to treat stroke, cerebral ischemia, qi deficiency, and hypertension. Buyang Huanwu decoction is traditionally used to treat stroke in China for more than 200 years and has a significant effect on cerebral ischemia, and RAP is monarch medicine of Buyang Huanwu decoction. Therefore, this study was designed to observe the regulatory effect of RAP on transmembrane iron transporters and ferroptosis-related factors in cerebral ischemia-reperfusion injury (CIRI) in rats. Methods: Middle cerebral artery occlusion (MCAO) was used to block blood flow in the blood supply area of the middle cerebral artery in seventy male SD rats to induce focal CIRI to establish a rat model of CIRI. RAP was administered to explore the regulatory effect of RAP on iron transmembrane transport under the condition of CIRI. The infarct size was measured using 2,3,5-triphenyl-tetrazolium chloride (TTC) staining, the pathological structure of brain tissue was observed by HE staining, and neuronal injury was evaluated by Nissl staining after treatment. Then, changes in the iron transporters ferritin (Fn), ferritin heavy chain (FHC), ferritin light chain (FLC), transferrin (Tf), transferrin receptor (TfR), divalent metal transporter 1 (DMT1), L-type calcium channel (LTCC), transient receptor potential canonical 6 (TRPC6), and ferroportin 1 (FPN1) were observed by immunohistochemistry staining (IHC) and Western blotting. The expression of key factors of ferroptosis, including the membrane sodium-dependent cystine/glutamate antiporter System Xc- (System Xc-) light chain subunit (XCT) and heavy chain subunit (SLC3A2), glutathione peroxidase 4 (GPX4), nuclear factor erythroid 2-related factor (NRF2), heme oxygenase-1 (HO-1), and iron-responsive element-binding protein 2 (IREB2) in the brain tissues of rats was assessed by Western blotting. RAP decreased the infarct size and neuronal injury after CIRI in rats. Similarly, RAP treatment regulated the expression of iron transporters. As such, RAP was able to reduce the expression of Fn, FHC, FLC, Tf, TfR, DMT1, and TRPC6 and increase the expression of FPN1 through a Tf/TfR-independent pathway after CIRI in rats. Conclusion: RAP stimulation inhibited ferroptosis by regulating the expression of the key ferroptosis factors XCT, SLC3A2, GPX4, NRF2, HO-1, and IREB2. In conclusion, RAP regulates transmembrane iron transport and ferroptosis to improve CIRI.

Gynostemma pentaphyllum polysaccharides ameliorate non-alcoholic steatohepatitis in mice associated with gut microbiota and the TLR2/NLRP3 pathway.

Recent studies have revealed the pivotal role of gut microbiota in the progress of liver diseases including non-alcoholic steatohepatitis (NASH). Many natural herbs, such as Gynostemma pentaphyllum (GP), have been extensively applied in the prevention of NASH, while the bioactive components and underlying mechanism remain unclear. The aim of this study was to investigate whether the polysaccharides of GP (GPP) have a protective effect on NASH and to explore the potential mechanism underlying these effects. C57BL/6 male mice were fed with a methionine-choline-deficient (MCD) diet for 4 weeks to induce NASH and administered daily oral gavage of sodium carboxymethylcellulose (CMC-Na), low dose of GPP (LGPP), high dose of GPP (HGPP), and polyene phosphatidylcholine capsules (PPC), compared with the methionine-choline-sufficient (MCS) group. Our results showed that the symptoms of hepatic steatosis, hepatocyte ballooning, liver fibrosis, and oxidative stress could be partially recovered through the intervention of GPP with a dose-dependent effect. Furthermore, gut microbiome sequencing revealed that HGPP altered the composition of gut microbiota, mainly characterized by the enrichment of genera including Akkermansia, Lactobacillus, and A2. Moreover, hepatic transcriptome analysis indicated that the anti-inflammatory effect of HGPP might be associated with toll-like receptor (TLR) and nod-like receptor (NLR) signaling pathways. HGPP could inhibit the expression of TLR2 and downregulate the expression of the NLRP3 inflammasome, as well as the pro-inflammatory cytokine tumor necrosis factor (TNF)-α and interleukin (IL)-1ß. In summary, GPP could ameliorate NASH possibly mediated via the modulation of gut microbiota and the TLR2/NLRP3 signaling pathway, indicating that GPP could be tested as a prebiotic agent in the prevention of NASH.

Spectrum-effect relationship between hplc fingerprint and anti-inflammatory activity of n-butanol parts of Tetrastigma planicaule (Hook) Gagnep.

The present study aimed to evaluate the spectrum-effect relationships between high-performance liquid chromatography fingerprints and anti-inflammatory effects of Tetrastigma planicaule(Hook.)Gagnep. Chemical fingerprints of ten batches of Tetrastigma planicaule from various sources were obtained by HPLC. The anti-inflammatory activity was investigated by a model of ear swelling in mice caused by xylene and a model of cotton pellet granuloma. Hierarchical cluster analysis (HCA) results showed that all the samples were clustered into four categories, which was basically consistent with the principal component analysis (PCA) results. The results of the joint grey relational analysis (GRA) and partial least squares regression analysis (PLSR) showed that peaks 1, 2 and 12 were positively correlated with the anti-acute inflammatory effect (ear swelling) in mice, and peaks 3, 5, 6 and 11 were positively correlated with the anti-chronic inflammatory effect (cotton pellet granuloma) in mice. The anti-inflammatory effect of Tetrastigma planicaule is the result of the synergistic effect of multiple components, which provides a basis for further exploring the anti-inflammatory substances and quality evaluation of the herb.

Protective role of selenium on ammonia-mediated nephrotoxicity via PI3K/AKT/mTOR pathway: Crosstalk between autophagy and cytokine release.

Ammonia (NH3) is a hazardous substance to human and animal health. Selenium (Se) is an essential micronutrient with multiple health benefits. The present study aimed to verify whether and how Se supplementation has a protective role against NH3 mediated-nephrotoxicity in pigs. A Se-NH3 interaction model was established in pigs and the kidney samples were collected after a 30-day treatment period. The results showed that NH3 exposure inhibited the PI3K/AKT/mTOR pathway and enhanced the secretion of inflammatory cytokines to induce autophagy and inflammation. Se can regulate the PI3K/AKT/mTOR pathway and attenuate the secretion of inflammatory cytokines altered by NH3 to reduce autophagy and inflammation. In addition, Se co-treatment inhibited ROS production, elevated the activities of antioxidant systems, and increased the expression of 13 selenoproteins in pig kidneys caused by NH3 exposure. These results implied that L-selenomethionine can moderate NH3-induced nephrotoxicity in pigs. Our study gives new ideas for the specific mechanism of NH3 nephrotoxicity and provides a reference for comparative medicine and clinical medication.

New enantiomeric lignans and new meroterpenoids with nitric oxide release inhibitory activity from Piper puberulum.

Six new lignans with various type of linkage between two C6-C3 fragments (1a, 1b, 2a, 2b, 3, 4), two new meroterpenoids (5, 6) and 24 known compounds (7-30) were isolated from an EtOH extract of the stems and leaves of Piper puberulum. The absolute configurations of enantiomers 1a and 1b were determined by single-crystal X-ray diffraction analysis, 2a and 2b were determined by comparing their calculated and experimental ECD spectra. Biogenetically, all the new lignans may come from the polymerization of two molecules of hydroxychavicol (30). In the anti-neuroinflammation activity assay, the IC50 values of fifteen compounds were lower than those of the positive control minocycline, and compound 1a showed good activity, but its enantiomer 1b showed no activity. Compound 1a have notable anti-neuroinflammatory activity, and can significantly decrease mRNA levels of proinflammatory cytokines (IL-1ß, IL-6, TNF-α) in a dose-dependent manner.

Selenomethionine protects against ammonia-induced apoptosis through inhibition of endoplasmic reticulum stress in pig kidneys.

Ammonia (NH3) emission is a common threat to farm animals. Selenium (Se) is known for its antioxidant property and can resist several stressors affecting farm animals. The aims of this study were (Ⅰ) to determine how excess NH3 exert nephrotoxic effects in pigs and (Ⅱ) to investigate whether selenomethionine has an alleviative effect on NH3 toxicity. Two diets supplemented with different doses of Se (0.22 mg/kg or 0.50 mg/kg) and two concentrations of NH3 (< 5 mg/m3 or 89.8 mg/m3) were used in a 2 × 2 factorial design trial for a period of 30 days. The results showed that NH3 exposure caused apoptosis and increased the number of apoptotic cells in pig kidneys. Further, the activities of antioxidant enzymes were decreased, and the transcriptional and translational levels of endoplasmic reticulum stress-related genes, Bcl-2 and Caspase family members were increased under NH3 exposure. In addition, Wnt/ß-catenin signaling pathway was suppressed after NH3 treatment. Dietary supplement with selenomethionine appears to offer protection against NH3-induced kidney injury in pigs and the pathologic changes above were alleviated. Our findings provide additional insight into the mechanism of NH3 toxicity in pigs while elucidating the role of Se as a potential antidote against NH3 poisoning.

[Quantitation and content investigation of bilirubin in cultured cow-bezoar].

A determination method for bilirubin in cultured cow-bezoar was developed in this study, with which the bilirubin in 15 batches of samples was quantified. The samples were first processed with 10% oxalic acid solution for the conversion of bilirubin from conjugated to unconjugated, followed by the extraction with dichloromethane. Then the obtained sample solutions were analyzed at 450 nm by HPLC[chromatographic column: Agilent TC-C_(18)(4.6 mm × 250 mm, 5 µm); mobile phase: acetonitrile and 1% glacial acetic acid aqueous solution(95∶5); flow rate: 1.0 mL·min~(-1)]. The bilirubin content in the 15 batches of cultured cow-bezoar was ranged from 21.9% to 41.7% with the average of 32.4%. The proposed method is accurate and reliable, thus making it suitable for the quantitation of bilirubin in cultured cow-bezoar and its quality assessment and control.

Dietary Soybean Oil Supplementation Affects Keel Bone Characters and Daily Feed Intake but Not Egg Production and Quality in Laying Hens Housed in Furnished Cages.

To evaluate dietary soybean oil supplementation on production performance, egg quality, and keel bone health in laying hens. Two hundred and four laying hens at 20 weeks of age (WOA) were distributed into 12 cages containing 17 birds each. Birds were either fed a commercial diet (control group, CON) or a diet supplemented with 3% of soybean oil (SO group). Experiments lasted 17 weeks. Body weight, daily feed intake, production performance and egg quality were measured at 25, 29, 33, and 37 WOA. Birds were subsequently assessed for keel bone status by palpation, and keel was excised to measure bone length, microstructure, bone mineral density (BMD), elements contents, and the expression of osteoprotegerin (OPG), receptor activator of nuclear factor kappa-B ligand (RANKL), collagen type II alpha 1 (COL2α1), periostin (POSTN), and sclerostin (SOST). The results showed that dietary SO supplementation did not affect production performance and egg quality (P > 0.05), but improved body weight of hens at 29 and 37 WOA (P < 0.05), and decreased daily feed intake at 33 and 37 WOA (P < 0.05). Incidence of keel bone damage (especially fracture) was higher in hens of SO group. Keel bone length in birds of SO group was significantly decreased compared to CON (P < 0.05). Keel bone of supplemented hens showed increased trabecular separation at 29 WOA and higher levels of V, Mn, Fe, Se, and Ba at 33 WOA (P < 0.05). Moreover, decreased BMD, trabecular number and thickness were observed in keel bone of laying hens receiving supplementation at 29 and 37 WOA (P < 0.05); decreased levels of Li, Ca, Hg, and TI at 33 WOA and trabecular thickness at 37 WOA (P < 0.05) were also identified. mRNA levels of SOST and RANKL and the ratio of RANKL/OPG mRNA levels were increased in birds fed a SO-supplemented diet (P < 0.05); COL2α1, OPG, and POSTN were downregulated at all sampling points (P < 0.05). Taken together, results indicate that feeding laying hens a diet supplemented with soybean oil can decrease daily feed intake and impair keel bone health but not influence production performance and egg quality.

Efficacy and safety of Chinese medicine for obstructive sleep apnea: A protocol for systematic review and meta-analysis.

BACKGROUND: Obstructive sleep apnea (OSA) is significant public concern. Clinical practice indicates that Chinese medicine has certain therapeutic advantages, while there is a lack of evidence-based medicine support. The aim of this study is to synthesize related data to explore efficacy and safety of Chinese medicine for OSA. METHODS: Data in PubMed, Embase, Web of Science, CNKI, WanFang, VIP databases were comprehensively searched. All the randomized controlled trials (RCTs) in OSA children were identified, in which the effects of Chinese medicine on a range of outcomes were compared. The search had a deadline of January 1, 2020. Two investigators independently conducted data extraction and assessed the literature quality of the included studies. The Revman5.3 software was used for meta-analysis of the included literature. RESULTS: The efficacy and safety of Chinese medicine for OSA were evaluated in terms of apnea hypopnea index (AHI, the average and lowest blood oxygen, the Epworth Sleep Scale [ESS], and adverse effects). CONCLUSIONS: This study provides reliable evidence-based support for the clinical application of Chinese medicine for OSA. PROSPERO REGISTRATION NUMBER: CRD42020154864.

Tripterine: A Potential Anti-Allergic Compound.

BACKGROUND: Tripterine (TRI), an active monomer in Tripterygium wilfordii, has significant pharmacological activities, such as anti-inflammatory, immunosuppressive and anti-tumor activities. TRI may be used to treat allergic diseases because of its characteristics of immunosuppression. OBJECTIVE: This study aims to explore the anti-allergic effect of TRI. METHODS: It was tested in vivo and in vitro in this study. RESULTS: The results showed that TRI could significantly inhibit histamine release from rat peritoneal mast cells; the inhibitory effect of TRI on histamine release was stronger than that of other known histamine inhibitors such as disodium cromoglyceride. TRI also significantly inhibited systemic anaphylactic shock induced by compound 48/80 and skin allergy induced by IgE, and inhibited the expression of inflammatory factors secreted by Human Mast Cells (HMC-1) induced by Phorbol 12-Myristate 13- Acetate (PMA) and calcium carrier A23187. In the animal model of allergic rhinitis induced by Ovalbumin (OA), the scores of friction, histamine, IgE, inflammatory factors and inflammatory cells decreased after TRI was administered orally or nasally. CONCLUSION: TRI, as an active immunoregulatory factor, has great potential in the treatment of mast cell-mediated allergic diseases.