Compound probiotics regulate the NRF2 antioxidant pathway to inhibit aflatoxin B1-induced autophagy in mouse Sertoli TM4 cells.

This study investigated the effects of compound probiotics (CP) on AFB1-induced cytotoxicity in Sertoli TM4 cells. The L9 (3 × 3) orthogonal test was conducted to determine the optimal CP required for high AFB1 degradation in the artificial gastrointestinal fluid in vitro. The maximal AFB1 degradation rate was 40.55 % (P < 0.05) when the final viable count was 1.0 × 105 CFU/mL for Bacillus subtilis, Lactobacillus casein, and Saccharomyces cerevisiae. The effects of CP and the CP supernatant (CPS) on TM4 cell viability were evaluated to achieve the optimal protective conditions. When CPS4 (corresponding to CP viable counts of 1.0 × 104 CFU/mL) was added to the TM4 cells for 24 h, the cell viability reached 108.86 % (P < 0.05). AFB1 reduced TM4 cell viability in a concentration- and time-dependent manner at an AFB1 concentration ranging from 0 to 1.5 µM after 48-h AFB1 exposure. The optimal AFB1 concentration/times for low- and high damage models were 0.5 and 1.25 µM both for 24 h, which decreased viability to 76.04 % and 65.35 %, respectively. however, CPS4 added to low- and high-damage models increased the cell viability to 97.43 % and 75.12 %, respectively (P < 0.05). Transcriptome sequencing was performed based on the following designed groups: the control, 0.5 µM AFB1, 1.25 µM AFB1, CPS4, and CPS4+0.5 µM AFB1. The Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis was further performed to identify significantly enriched signaling pathways, which were subsequently verified. It was shown that AFB1 induced apoptosis by blocking the PI3K-AKT-mTOR pathway and upregulating autophagy proteins such as LC3B, Beclin1, and ATG5 while inhibiting autophagic flux. CPS4 promoted AFB1 degradation, activated the p62-NRF2 antioxidant, and inhibited ROS/TRPML1 pathways, thereby reducing ROS production and inflammation and ultimately alleviating AFB1-induced autophagy and apoptosis. These findings supports the potential of probiotics to protect the male reproductive system from toxin damage.

Palmitic acid induces ß-cell ferroptosis by activating ceramide signaling pathway.

Individuals with type 2 diabetes mellitus frequently display heightened levels of palmitic acid (PA) in their serum, which may lead to ß-cell damage. The involvement of ferroptosis, a form of oxidative cell death in lipotoxic ß-cell injury remains uncertain. Here, we have shown that PA induces intracellular lipid peroxidation, increases intracellular Fe2+ content and decreases intracellular glutathione peroxidase 4 (GPX4) expression. Furthermore, PA causes distinct changes in pancreatic islets and INS-1 cells, such as mitochondrial atrophy and increased membrane density. Furthermore, the presence of the ferroptosis inhibitor has a significant mitigating effect on PA-induced ß-cell damage. Mechanistically, PA increased ceramide content and c-Jun N-terminal kinase (JNK) phosphorylation. The ceramide synthase inhibitor effectively attenuated PA-induced ß-cell damage and GPX4/Fe2+ abnormalities, while inhibiting JNK phosphorylation. Additionally, the JNK inhibitor SP600125 improved PA-induced cell damage. In conclusion, by promoting ceramide synthesis, PA inhibited GPX4 expression and increased intracellular Fe2+ to induce ß-cell ferroptosis. Moreover, JNK may be a downstream mechanism of ceramide-triggered lipotoxic ferroptosis in ß-cells.

Transparent cap adjusted the stent placed for stenosis after endoscopic injection of esophageal varices: A case report.

BACKGROUND: The stent embedded in the esophageal mucosa is one of the complications after stenting for esophageal stricture. We present a case of stent adjustment with the aid of a transparent cap after endoscopic injection of an esophageal varices stent. CASE SUMMARY: A 61-year-old male patient came to the hospital with discomfort of the chest after the stent implanted for the stenosis because of endoscopic injection of esophageal varices. The gastroscopy was performed, and the stent embedded into the esophageal mucosa. At first, we pulled the recycling line for shrinking the stent, however, the mucosa could not be removed from the stent. Then a forceps was performed to remove the mucosa in the stent, nevertheless, the bleeding form the mucosa was obvious. And then, we used a transparent cap to scrape the mucosa along the stent, and the mucosa were removed successfully without bleeding. CONCLUSION: A transparent cap helps gastroscopy to remove the mucosa embedded in the stent after endoscopic injection of the esophageal varices stent.

Corn straw-saccharification fiber improved the reproductive performance of sows in the late gestation and lactation via lipid metabolism.

With the development of animal husbandry, the shortage of animal feedstuffs has become serious. Dietary fiber plays a crucial role in regulating animal health and production performance. The aim of this study was to investigate the effects of three kinds of corn straw-saccharification fibers (CSSF) such as high-fiber and low-saccharification (HFLS), medium-fiber and medium-saccharification (MFMS), low-fiber and high-saccharification (LFHS) CSSF on the reproductive performance of sows. Thirty-two primiparous Yorkshire sows were randomly assigned to 4 groups, 8 sows for each group. Group A was the basal diet as the control group; groups B - D were added with 6% HFLSCSSF, 6% MFMSCSSF and 6% LFHSCSSF to replace some parts of corn meal and wheat bran in the basal diet, respectively. The experimental period was from day 85 of gestation to the end of lactation (day 25 post-farrowing). The results showed that 6% LFHSCSSF addition significantly increased number of total born (alive) piglets, litter weight at birth (p < 0.05), whereas three kinds of CSSF significantly decreased backfat thickness of sows during gestation (p < 0.001), compared with the control group. Furthermore, CSSF improved the digestibility of crude protein, ether extract and fiber for sows. In addition, the levels of total cholesterol, total triglycerides, and high-density lipoprotein cholesterol in serum of sows were decreased by different kinds of CSSF. Further analysis revealed that CSSF regulated lipid metabolism through adjusting the serum metabolites such as 4-pyridoxic acid, phosphatidyl cholines and L-tyrosine. In summary, CSSF addition to the diets of sows during late gestation and lactation regulated lipid metabolism and improved reproductive performance of sows. This study provided a theoretical basis for the application of corn straw in sow diets.

Dynamical behaviours of discrete amensalism system with fear effects on first species.

Amensalism, a rare yet impactful symbiotic relationship in ecological systems, is the focus of this study. We examine a discrete-time amensalism system by incorporating the fear effect on the first species. We identify the plausible equilibrium points and analyze their local stability conditions. The global attractivity of the positive equilibrium, $ E^* $, and the boundary equilibrium, $ E_1 $, are analyzed by exploring threshold conditions linked to the level of fear. Additionally, we analyze transcritical bifurcations and flip bifurcations exhibited by the boundary equilibrium points analytically. Considering some biologically feasible parameter values, we conduct extensive numerical simulations. From numerical simulations, it is observed that the level of fear has a stabilizing effect on the system dynamics when it increases. It eventually accelerates the extinction process for the first species as the level of fear continues to increase. These findings highlight the complex interplay between external factors and intrinsic system dynamics, enriching potential mechanisms for driving species changes and extinction events.

Mitogen-activated protein kinases MPK3 and MPK6 phosphorylate receptor-like cytoplasmic kinase CDL1 to regulate soybean basal immunity.

Soybean cyst nematode (SCN; Heterodera glycines Ichinohe), one of the most devastating soybean (Glycine max) pathogens, causes significant yield loss in soybean production. Nematode infection triggers plant defense responses; however, the components involved in the upstream signaling cascade remain largely unknown. In this study, we established that a mitogen-activated protein kinase (MAPK) signaling module, activated by nematode infection or wounding, is crucial for soybeans to establish SCN resistance. GmMPK3 and GmMPK6 directly interact with CDG1-LIKE1 (GmCDL1), a member of the receptor-like cytoplasmic kinase (RLCK) subfamily VII. These kinases phosphorylate GmCDL1 at Thr-372 to prevent its proteasome-mediated degradation. Functional analysis demonstrated that GmCDL1 positively regulates immune responses and promotes SCN resistance in soybeans. GmMPK3-mediated and GmMPK6-mediated phosphorylation of GmCDL1 enhances GmMPK3 and GmMPK6 activation and soybean disease resistance, representing a positive feedback mechanism. Additionally, 2 L-type lectin receptor kinases, GmLecRK02g and GmLecRK08g, associate with GmCDL1 to initiate downstream immune signaling. Notably, our study also unveils the potential involvement of GmLecRKs and GmCDL1 in countering other soybean pathogens beyond nematodes. Taken together, our findings reveal the pivotal role of the GmLecRKs-GmCDL1-MAPK regulatory module in triggering soybean basal immune responses.

Deciphering tumor immune microenvironment differences between high-grade serous and endometrioid ovarian cancer to investigate their potential in indicating immunotherapy response.

BACKGROUND: Ovarian cancer is a significant public health concern with a poor prognosis for epithelial ovarian cancer. To explore the potential of immunotherapy in treating epithelial ovarian cancer, we investigated the immune microenvironments of 52 patients with epithelial ovarian cancer, including 43 with high-grade serous ovarian cancer and 9 with endometrioid ovarian cancer. RESULTS: Fresh tumor tissue was analyzed for genetic mutations and various parameters related to immune evasion and infiltration. The mean stromal score (stromal cell infiltration) in high-grade serous ovarian cancer was higher than in endometrioid ovarian cancer. The infiltration of CD8 T cells and exhausted CD8 T cells were found to be more extensive in high-grade serous ovarian cancer. Tumor Immune Dysfunction and Exclusion scores, T cell exclusion scores, and cancer-associated fibroblasts (CAF) scores were also higher in the high-grade serous ovarian cancer group, suggesting that the number of cytotoxic lymphocytes in the tumor microenvironment of high-grade serous ovarian cancer is likely lower compared to endometrioid ovarian cancer. CONCLUSIONS: The high mean stromal score and more extensive infiltration and exhaustion of CD8 T cells in high-grade serous ovarian cancer indicate that high-grade serous ovarian cancer exhibits a higher level of cytotoxic T cell infiltration, yet these T cells tend to be in a dysfunctional state. Higher Tumor Immune Dysfunction and Exclusion scores, T cell exclusion scores, and CAF scores in high-grade serous ovarian cancers suggest that immune escape is more likely to occur in high-grade serous ovarian cancer, thus endometrioid ovarian cancer may be more conducive to immunotherapy. Therefore, it is crucial to design immunotherapy clinical trials for ovarian cancer to distinguish between high-grade serous and endometrioid ovarian cancer from the outset. This distinction will help optimize treatment strategies and improve outcomes for patients with different subtypes.

Cholesterol metabolism in T-cell aging: Accomplices or victims.

Aging has a significant impact on the function and metabolism of T cells. Cholesterol, the most important sterol in mammals, is known as the "gold of the body" because it maintains membrane fluidity, rigidity, and signal transduction while also serving as a precursor of oxysterols, bile acids, and steroid hormones. Cholesterol homeostasis is primarily controlled by uptake, biosynthesis, efflux, and regulatory mechanisms. Previous studies have suggested that there are reciprocal interactions between cholesterol metabolism and T lymphocytes. Here, we will summarize the most recent advances in the effects of cholesterol and its derivatives on T-cell aging. We will furthermore discuss interventions that might be used to help older individuals with immune deficiencies or diminishing immune competence.

Case report: Long-read sequencing identified a novel 14.9-kb deletion of the α-globin gene locus in a family with α-thalassemia in China.

Background: Thalassemia is a hereditary blood disease resulting from globin chain synthesis impairment because of α- and/or ß-globin gene variants. α-thalassemia is characterized by non-deletional and deletional variants in the HBA gene locus, of which rare deletional variants are difficult to detect by conventional polymerase chain reaction (PCR)-based methods. Case report: We report the case of a one-month-old boy, who and his mother had abnormal hematological parameters, while his father had normal hematology. Conventional PCR-reverse dot blot (RDB) was performed for all family members to analyze the 23 most common thalassemia variants in China, but did not identify any pathologic variants. Single-molecule real-time (SMRT) long-read sequencing (LRS) technology was then performed and identified an unreported 14.9-kb large deletion (hg38 chr16:168,803-183,737) of the α-globin gene locus, which disrupted both HBA1 and HBA2 genes in the proband and his mother. The exact breakpoints of the deletion were confirmed by gap-PCR and Sanger sequencing. Conclusion: We have detected a novel large deletion in α-globin gene locus in China, which not only enriches the variant spectrum of thalassemia, but also demonstrates the accuracy and efficiency of LRS in detecting rare and novel deletions.

Large intramural hematoma of the esophagus after endoscopic injection sclerotherapy: A case report.

RATIONALE: Endoscopic injection sclerotherapy (EIS) is a common treatment for patients with liver cirrhosis and esophageal varices. It can effectively treat variceal rupture and bleeding caused by liver cirrhosis. However, EIS has many complications, including postoperative bleeding, retrosternal pain, esophageal ulcers, esophageal stenosis, and ectopic embolism. Intramural hematoma of the esophagus (IHE) is a rare complication of EIS that can lead to chest tightness, chest pain, and dysphagia. PATIENTS CONCERNS: A 55-year-old man developed severe nausea and vomiting accompanied by chest pain after EIS. DIAGNOSIS: Comprehensive imaging features, the patient was diagnosed as IHE. INTERVENTIONS: A vascular clamp was used for hemostasia, and a feeding tube was placed in the patient's jejunum. OUTCOMES: After the removal of the jejunal feeding tube and the intake of a semiliquid diet, the patient had no episodes of chest pain, chest tightness, or dysphagia and was discharged after 2 days of observation. LESSONS: Although IHE rarely occurs after EIS, we should not overlook its risk. The occurrence of IHE is not directly related to the number of EISs received or the degree of liver cirrhosis but is more likely related to postoperative nausea and vomiting. Therefore, timely medication and observation are particularly important for patients with nausea and vomiting after endoscopic treatment.

Effects of compound feed additive on growth performance and intestinal microbiota of broilers.

The purpose of this experiment was to determine the effectiveness of compound feed additive (CFA) to replace antibiotics for broiler production. A total of 350 one-day-old Arbor Acres broilers were randomly divided into 7 groups, 5 replications in each group and 10 broilers in each replication. Group A was the control; group B was supplemented with 75 mg/kg chlortetracycline; groups C, D, and E were supplemented with 0.03, 0.06, and 0.09% CFA including glucose oxidase, curcumin, and Lactobacillus acidophilus; group F was supplemented with 0.03% CFA plus 0.50% glucose; group G was supplemented with 0.50% glucose. The feeding period was divided into the early (1-21 d) and later stages (22-42 d). The results showed that average daily gain (ADG) and feed conversion rate (F/G) in group F in later stage were significantly better than those in the control and antibiotic groups; the diarrhea rates in the groups containing CFA in both stages was significantly lower than that in the control and antibiotic groups, indicating that CFA was better than antibiotics to improve growth and decrease diarrhea rate for broilers. Pathogenic E. coli challenge significantly increased diarrhea rates and decreased ADG for broilers; however, CFA addition could alleviate the above negative responses by increasing gut Lactobacillus abundance and decreasing Shigella abundance. It can be concluded that CFA can replace antibiotics to regulate intestinal microbiota, reduce diarrhea rate, and improve broiler growth.

Compound mycotoxin detoxifier alleviating aflatoxin B1 toxic effects on broiler growth performance, organ damage and gut microbiota.

The aim of this study was to evaluate the effects of compound mycotoxin detoxifier (CMD) on alleviating the toxic effect of aflatoxin B1 (AFB1) for broiler growth performance. One-kilogram CMD consists of 667 g aflatoxin B1-degrading enzyme (ADE, 1,467 U/g), 200 g montmorillonite and 133 g compound probiotics (CP). The feeding experiment was divided into 2 stages (1-21 d and 22-42 d). In the early stage, a total of 300 one-day-old Ross broilers were randomly divided into 6 groups, 5 replications for each group, 10 broilers (half male and half female) in each replication. In the later feeding stage, about 240 twenty-two-day-old Ross broilers were randomly divided into 6 groups, 8 replications for each group, 5 broilers in each replication. Group A: basal diet; group B: basal diet with 40 µg/kg AFB1; group C: basal diet with 1 g/kg CMD; groups D, E, and F: basal diet with 40 µg/kg AFB1 plus 0.5, 1.0 and 1.5 g/kg CMD, respectively. The results indicated that AFB1 significantly decreased average daily gain (ADG), protein metabolic rate, organ index of thymus, bursa of Fabricius (BF), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) and catalase activities in serum, and increased AFB1 residues in serum and liver (P < 0.05). Hematoxylin-Eosin (HE) staining analysis of jejunum, liver and kidney showed that AFB1 caused the main pathological changes with different degrees of inflammatory cell infiltration. However, CMD additions could alleviate the negative effects of AFB1 on the above parameters. The gut microbiota analysis indicated that AFB1 could significantly increase the abundances of Staphylococcus-xylosu, Esherichia-coli-g-Escherichia-Shigella, and decrease Lactobacillus-aviarius abundance (P < 0.05), but which were adjusted to almost the same levels as the control group by CMD addition. The correlative analysis showed that Lactobacillus-aviarius abundance was positively correlated with ADG, SOD and BF (P < 0.05), whereas Staphylococcus-xylosus abundance was positively correlated with AFB1 residues in serum and liver (P < 0.05). In conclusion, CMD could keep gut microbiota stable, alleviate histological lesions, increase growth performance, and reduce mycotoxin toxicity. The optimal CMD addition should be 1 g/kg in AFB1-contaminated broilers diet.

Antimicrobial peptide hepcidin contributes to restoration of the intestinal flora after Aeromonas hydrophila infection in Acrossocheilus fasciatus.

Hepcidin is a cysteine-rich antimicrobial peptide that serves an important role in the immunity system of fishes. It exhibits antibacterial, antifungal, antiviral, and antitumor activities. However, the exact role of fish hepcidin in the regulation of the intestinal flora still remains a mystery. In our study, we sequenced and characterized hepcidin from the liver of Acrossocheilus fasciatus. Phylogenetic tree analysis showed that A. fasciatus hepcidin and Gobiocypris rarus hepcidin were the most closely related, and both belonged to the fish HAMP1 cluster. Studies conducted on in vivo tissue distribution showed that the expression of hepcidin was highest in healthy A. fasciatus liver. Aeromonas hydrophila infection was confirmed by the increased expression of pro-inflammatory cytokine genes and bacterial loads in A. fasciatus tissues. After A. hydrophila infection, hepcidin expression significantly increased in the liver, spleen, and head kidney. In vitro antibacterial assays showed that hepcidin exhibits strong broad spectrum antibacterial activity. Furthermore, we examined the regulatory effect of hepcidin on the intestinal flora and found that A. fasciatus hepcidin restored the reduced diversity and compositional changes in intestinal flora caused by A. hydrophila infection. Our results suggest that hepcidin could regulate the intestinal flora in fishes; however, the underlying mechanisms need to be explored in greater detail.

Co-training based virtual sample generation for solving the small sample size problem in process industry.

With the development of industrialization, the production scale and complexity of process industries are getting larger and larger. But, limited by the small amounts of samples and the uneven sample distribution in the process industry, it is difficult to establish accurate and efficient data-driven soft sensor models to predict some variables. To further develop the application of soft sensor models, generating new virtual samples based on the original sample distribution to extend the sample set is an ideal approach to solve this problem. In this paper, a novel virtual sample generation method based on the co-training of two K-Nearest Neighbor (KNN) models is proposed. First, according to the sparse parameter, sparse regions in each dimension of the feature space are identified. Second, the input features of virtual samples are generated in these sparse regions by performing interpolation operations. Third, the outputs of virtual samples are predicted by double KNN regressors based on co-training. The qualified virtual samples are screened and the model is updated using these virtual samples to improve the prediction accuracy of the double KNN models. To verify the effectiveness and superiority of the proposed virtual sample generation method based on the co-training (CTVSG), case studies are conducted using two standard functions and a Purified Terephthalic Acid (PTA) industrial dataset, where the effectiveness of CTVSG is confirmed.

Comparative Metabolomic Profiling Reveals Key Secondary Metabolites Associated with High Quality and Nutritional Value in Broad Bean (Vicia faba L.).

High quality and nutritional benefits are ultimately the desirable features that influence the commercial value and market share of broad bean (Vicia faba L.). Different cultivars vary greatly in taste, flavor, and nutrition. However, the molecular basis of these traits remains largely unknown. Here, the grain metabolites of the superior Chinese landrace Cixidabaican (CX) were detected by a widely targeted metabolomics approach and compared with the main cultivar Lingxiyicun (LX) from Japan. The analyses of global metabolic variations revealed a total of 149 differentially abundant metabolites (DAMs) were identified between these two genotypes. Among them, 84 and 65 were up- and down-regulated in CX compared with LX. Most of the DAMs were closely related to healthy eating substances known for their antioxidant and anti-cancer properties, and some others were involved in the taste formation. The KEGG-based classification further revealed that these DAMs were significantly enriched in 21 metabolic pathways, particularly in flavone and flavonol biosynthesis. The differences in key secondary metabolites, including flavonoids, terpenoids, amino acid derivates, and alkaloids, may lead to more nutritional value in a healthy diet and better adaptability for the seed germination of CX. The present results provide important insights into the taste/quality-forming mechanisms and contributes to the conservation and utilization of germplasm resources for breeding broad bean with superior eating quality.

Transcriptomic analysis of intermuscular bone development in barbel steed (Hemibarbus labeo).

Intermuscular bones (IBs), which are little, bony spicules in muscle, are embedded in lower teleosts' myosepta. Despite the importance of studying IB development in freshwater aquaculture species, the genes associated with IB development need to be further explored. In the present study, we identified four stages of IB development in barbel steed (Hemibarbus labeo), namely stage 1: IBs have not emerged, stage 2: a few small IBs have emerged in the tail, stage 3: longer IBs gradually emerged in the tail and stage 4: all of the IBs in the tail are mature and long, via Alizarin red staining. Subsequently, we used the HiseqXTen platform to sequence and de novo assemble the transcriptome of epaxial muscle (between 35th and 40th myomere) of barbel steed at 29 days (stage 1) and 42 days (stage 3) after hatching. A total of 190,814 unigenes were obtained with an average length and N50 of 648 bp and 1027 bp, respectively. We found 2174 differentially expressed genes (DEGs) between stages 1 and 3, of which 378 and 1796 were up- and down-regulated, respectively. Functional enrichment analysis showed that several DEGs functioned in ossification, positive regulation of osteoblast differentiation, osteoblast differentiation, and BMP signaling pathway, and were further enriched in signal pathway, including osteoclast differentiation, TGF-ß signaling pathway, cytokine-cytokine receptor interaction, Jak-STAT signaling pathway, and other KEEG pathways. In conclusion, we identified genes that may be related to IB development, such as kazal type serine peptidase inhibitor domain 1 (KAZALD1), extracellular matrix protein 1 (ECM1), tetranectin, bone morphogenetic protein 1 (bmp1), acid phosphatase 5 (ACP5), collagen type XI alpha 1 chain (COL11A1), matrix metallopeptidase 9 (MMP9), pannexin-3 (PANX3), sp7 transcription factor (Sp7), and c-x-c motif chemokine ligand 8 (CXCL8), by comparing the transcriptomes of epaxial muscle before and after IB ossification. This study provided a theoretical basis for identifying the molecular mechanisms underlying IB development in fish.

Effects of Compound Mycotoxin Detoxifier on Alleviating Aflatoxin B1-Induced Inflammatory Responses in Intestine, Liver and Kidney of Broilers.

In order to alleviate the toxic effects of aflatoxins B1 (AFB1) on inflammatory responses in the intestine, liver, and kidney of broilers, the aflatoxin B1-degrading enzyme, montmorillonite, and compound probiotics were selected and combined to make a triple-action compound mycotoxin detoxifier (CMD). The feeding experiment was divided into two stages. In the early feeding stage (1−21 day), a total of 200 one-day-old Ross broilers were randomly divided into four groups; in the later feeding stage (22−42 day), 160 broilers aged at 22 days were assigned to four groups: Group A: basal diet (4.31 µg/kg AFB1); Group B: basal diet with 40 µg/kg AFB1; Group C: Group A plus 1.5 g/kg CMD; Group D: Group B plus 1.5 g/kg CMD. After the feeding experiment, the intestine, liver, and kidney tissues of the broilers were selected to investigate the molecular mechanism for CMD to alleviate the tissue damages. Analyses of mRNA abundances and western blotting (WB) of inflammatory factors, as well as immunohistochemical (IHC) staining of intestine, liver, and kidney tissues showed that AFB1 aggravated the inflammatory responses through NF-κB and TN-α signaling pathways via TLR pattern receptors, while the addition of CMD significantly inhibited the inflammatory responses. Phylogenetic investigation showed that AFB1 significantly increased interleukin-1 receptor-associated kinase (IRAK-1) and mitogen-activated protein kinase (MAPK) activities (p < 0.05), which were restored to normal levels by CMD addition, indicating that CMD could alleviate cell inflammatory damages induced by AFB1.

Effect of the Combined Compound Probiotics with Glycyrrhinic Acid on Alleviating Cytotoxicity of IPEC-J2 Cells Induced by Multi-Mycotoxins.

Aflatoxins B1 (AFB1), deoxynivalenol (DON) and zearalenone (ZEA) are the three most prevalent mycotoxins, whose contamination of food and feed is a severe worldwide problem. In order to alleviate the toxic effects of multi-mycotoxins (AFB1 + DON + ZEA, ADZ) on inflammation and apoptosis in swine jejunal epithelial cells (IPEC-J2), three species of probiotics (Bacillus subtilis, Saccharomyces cerevisiae and Pseudomonas lactis at 1 × 105 CFU/mL, respectively) were mixed together to make compound probiotics (CP), which were further combined with 400 µg/mL of glycyrrhinic acid (GA) to make bioactive materials (CGA). The experiment was divided into four groups, i.e., the control, ADZ, CGA and ADZ + CGA groups. The results showed that ADZ decreased cell viability and induced cytotoxicity, while CGA addition could alleviate ADZ-induced cytotoxicity. Moreover, the mRNA expressions of IL-8, TNF-α, NF-Κb, Bcl-2, Caspase-3, ZO-1, Occludin, Claudin-1 and ASCT2 genes, and protein expressions of TNF-α and Claudin-1 were significantly upregulated in ADZ group; while the mRNA abundances of IL-8, TNF-α, NF-Κb, Caspase-3, ASCT2 genes, and protein expressions of TNF-α and Claudin-1 were significantly downregulated in the ADZ + CGA group. In addition, the protein expressions of COX-2, ZO-1, and ASCT2 were significantly downregulated in the ADZ group, compared with the control group; whereas CGA co-incubation with ADZ could increase these protein expressions to recover to normal levels. This study indicated that CGA could alleviate cytotoxicity, apoptosis and inflammation in ADZ-induced IPEC-J2 cells and protect intestinal cell integrity from ADZ damages.

Effect of Neiyi Prescription of QIU on autophagy and angiogenic ability of endometriosis via the PPARγ/NF-κB signaling pathway.

OBJECTIVES: Neiyi Prescription of QIU (NYPQ) is a traditional Chinese medicine prescription for the treatment of endometriosis (EMS). Here, we aimed to examine the effects and mechanisms of NYPQ on angiogenic ability in EMS. STUDY DESIGN: EMS rats were established with estradiol valerate and autologous transplantation. EMS rats were intraperitoneally injected with chloroquine (CQ, 40 mg/kg), rapamycin (RAPA, 1 mg/kg), and monoclonal antibody VEGF (anti-VEGF, 3 mg/g/d) or administered 5, 10, 20 mg/g/d NYPQ decoction through oral gavage for 4 weeks, respectively. By the before and end of the treatment period, the volume of the endometriotic lesions was measured. The pathological morphology, angiogenesis, and the number of autophagosomes of the endometriotic lesion were observed by hematoxylin and eosin staining, immunohistochemistry, and transmission electron microscope, respectively. The cell viability, apoptosis, and angiogenesis of HUVECs were detected by MTT, flow cytometry, and lumen formation experiment, respectively. The expression levels of VEGF, autophagy-/apoptosis-/PPARγ/NF-κB- pathway-related proteins in endometrium tissues or HUVECs were detected by western blot assays. RESULTS: The autophagy agonist rapamycin reduced the lesion size, the microvessel density, and VEGF expression, and promoted the production of autophagosomes and the expression of autophagy-related proteins, while the autophagy inhibitor chloroquine had the opposite effects. In vivo, NYPQ could dose-dependently reduce lesion volume and microvessel density, ameliorate histopathological features and promote autophagosome production of ectopic endometrium. Moreover, serum-containing NYPQ could significantly inhibit the cell viability and tube formation of HUVECs and elevate HUVECs apoptosis. Besides, NYPQ significantly reduced VEGF and promoted autophagy-/apoptosis-related protein expressions. Also, NYPQ might promote autophagy and inhibit angiogenesis by activating the PPARγ/NF-κB pathway. CONCLUSIONS: Collectively, these findings indicate that NYPQ has therapeutic potential in experimentally induced peritoneal endometriosis, and its mechanism may be related to the activation of the PPARγ/NF-κB signaling pathway.