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Objective: To study the efficacy of 3 treatment options for type 2 cesarean scar pregnancy (CSP) and establish an optimal treatment strategy for type 2 CSP.Design: Retrospective cohort study.Setting: A tertiary hospital.Patients: The study examined 160 women with type 2 CSP.Interventions: Ultrasound-guided vacuum aspiration after local injection of lauromacrogol, ultrasound-guided vacuum aspiration after uterine artery embolization (UAE), and transabdominal resection or hysteroscopy combined with laparoscopic resection.Main Outcome Measures: The success rates, duration of hospitalization, hospitalization cost, amount of blood loss, recovery time, and menstruation resuming after recovery.Results: The success rates of the UAE, lauromacrogol, and surgical groups were 87.1%, 92.5%, and 95.5%, respectively, with no significant differences. The cost and duration of hospitalization in the lauromacrogol group were significantly lower than those in the UAE and surgical groups. Analysis of the causes of treatment failure revealed a significant difference in the gestational age. The area under the receiver operating characteristic curve was 0.660 (95% confidence interval, 0.533-0.788). When the gestational age was 48.5 days, Youden index was the highest. Furthermore, when the diagnostic thresholds were selected as 49, 56, and 63 days of pregnancy, the corresponding areas under the receiver operating characteristic curve were 0.652, 0.541, and 0.510, respectively.Conclusion: Ultrasound-guided vacuum aspiration after local injection of lauromacrogol is recommended for patients with type 2 CSP at <49 days of gestation. Laparotomy or laparoscopy combined with hysteroscopy is suitable for patients with gestation of >49 days, especially for those with >56 days of gestation. [ABSTRACT FROM AUTHOR]

Simple Summary: Aflatoxin B1 (AFB1) is widely present in animal feed as a mycotoxin, and it poses a serious threat to human and animal health. Curcumin (CUR) as a feed additive has been well documented for its antimicrobial, anti-inflammatory, antioxidant, and antiviral activities. The present experiment was designed to investigate the mitigating effect of CUR on the growth performance, liver, and intestinal health of broilers fed AFB1-contaminated diets. The results showed that CUR alleviated liver and intestinal damage in broilers caused by feeding AFB1-contaminated diets, and this damage was associated with the Nrf2 pathway. Notably, CUR also mitigated the changes in intestinal permeability caused by AFB1, which may be closely related to liver health (via the gut–liver axis). These results provide new ideas for future research on the therapeutic mechanism of CUR in alleviating AFB1 poisoning in broilers. This experiment aimed to investigate the mitigating effect of CUR on the growth performance and liver and intestinal health of broilers fed AFB1-contaminated diets. In this study, 320 one-day-old healthy male Arbor Acres (AA) broilers were randomly divided into four groups, including the Control group (fed the basal diet), the AFB1 group (fed the AFB1-contaminated diet containing 1 mg/kg AFB1), the AFB1+CUR group (fed the AFB1-contaminated diet with 500 mg/kg CUR), and the CUR group (fed the basal diet containing 500 mg/kg CUR), with eight replicates of ten animals per group and a 28 d experimental period. In terms of the growth performance, the addition of 500 mg/kg CUR significantly improved AFB1-induced significant reductions in the final body weight on day 28 and mean daily gain (p < 0.05) and increased the ratio of the mean daily feed intake to mean daily weight gain in broilers (p < 0.05). In terms of liver health, significant improvements in liver histological lesions occurred in broilers in the AFB1+CUR group compared to the AFB1 group, with significantly higher glutathione peroxidase (GSH-Px), catalase (CAT), and total superoxide dismutase (T-SOD) activities (p < 0.05) and significantly higher levels of nuclear factor erythroid 2-related factor 2 (Nrf2), Kelch-like ECH-associated protein 1 (Keap-1), heme oxygenase 1 (HO-1), and NAD(P)H quinone oxidoreductase 1 (NQO-1) gene expression (p < 0.05). In terms of intestinal health, CUR addition significantly increased the relative length of ileum (p < 0.05), significantly elevated the height of ileal villi (p < 0.05), significantly reduced D-Lactate (D-LA) and diamine oxidase (DAO) activities in broiler serum (p < 0.05), significantly increased GSH, CAT, and T-SOD activities in ileal tissues (p < 0.05), and significantly elevated the expression of Nrf2, HO-1, and NQO-1 genes (p < 0.05) compared to the AFB1 group. In conclusion, CUR showed a protective effect against damage to the liver and intestine caused by AFB1 in broilers through the Nrf2 signaling pathway, thereby improving the growth performance of broilers exposed to AFB1. [ABSTRACT FROM AUTHOR]

Background. Epithelial ovarian cancer (EOC) has the lowest survival rate among female reproductive cancers present with symptoms of aggressive malignancies, poor prognosis, drug resistance and postoperative recurrence. The majority of patients with EOC are diagnosed at an advanced stage due to the therapeutic challenges including lack of early diagnosis and effective therapeutic targets for EOC. Methods. Pan-cancer analyses were performed to explore the features of forkhead-box (FOX) A1 (FOXA1) using data from TCGA and GTEx databases. R package "clusterprofiler" was used to perform the enrichment analysis of FOXA1 in EOC. Data downloaded from Drug Sensitivity in Cancer (GDSC) database were used to evaluate the association between FOXA1 and antitumor drug sensitivity. In experimental verification, FOXA1 expression was detected using qRT-PCR and western blot assays. Western blot, immunofluorescence staining, and Transwell assays were used to assess the influence of FOXA1 silencing on epithelial-mesenchymal transition (EMT) of EOC cells. Results. We found that FOXA1 was highly expressed in EOC and predicted poorer survival of EOC patients. We observed that FOXA1 expression was positively correlated EMT-related pathways. Through experimental verification, we found the underlying function of FOXA1 to promote EMT in ovarian cancers. The results from western blot, immunofluorescence staining, and Transwell assays showed that FOXA1 silencing impeded the progression of EMT and invasiveness of the cancer cells. Furthermore, CCK-8 and invasion assays suggested that siRNA-FOXA1 attenuated the ability of cancer cells to metastasize and proliferate. Dual-luciferase reporter assays confirmed the binding activity of FOXA1 to the promoter of connective tissue growth factor (CTGF). In addition, we found that FOXA1 was closely correlated immunosuppressive microenvironment of EOC. High FOXA1 expression may contribute to the resistance of many anticancer drugs. Conclusions. Our results predict and validate the function of FOXA1 in promoting EMT and the progression of disease in EOC. Targeting FOXA1 may improve the sensitivity of EOC treatment. [ABSTRACT FROM AUTHOR]

Background: Acid-tolerant enteric pathogens can evade small intestinal acid barriers, colonize and infect the intestinal tract. However, broad-spectrum antibiotics are not the best therapeutic strategy because of the disruption of intestinal flora caused by its indiscriminate antimicrobial activity against beneficial and harmful bacteria. So that is what inspired us to combine pH regulation with nanotechnology to develop a pH-triggered site-targeted antimicrobial peptide with entrapping function. Results: A pH-triggered dual biological functional self-assembled peptide (SAP) was designed according to the features of amino-acid building blocks and the diagonal cation–π interaction principle. The results of characterization experiments showed that changes in pH conditions could trigger microstructural transformation of the nanopeptide from nanospheres to nanofibers. The subsequent antibacterial and toxicity experiments determined that SAP had great antimicrobial activity against Escherichia coli, Salmonella typhimurium, Listeria monocytogenes, and Bacillus cereus above 15.6 μg/mL under acidic conditions by disrupting bacterial membrane integrity, excellent biocompatibility in vitro even at 250 μg/mL and high tolerance in physical environment. Moreover, at peptide concentrations greater than 62.5 μg/mL, SAP showed the entrapment property, which played an important role in phagocytic clearance in infection forces. Meanwhile, the in vivo results revealed that SAP possessed excellent therapeutic effect and good biosafety. Conclusions: Our study revealed the antibacterial activity of a short β-hairpin forming self-assembled peptide, and established an innovative design strategy for peptide-based nanomaterials and a new treatment strategy for gastrointestinal bacterial infections. [ABSTRACT FROM AUTHOR]

Cathelicidin host defense peptides (cHDPs) widely exist in animals with the functions of innate immunity and acquired immunity. To investigate the tissue and sequential expression patterns of the dCATH gene, which encodes the only cHDPs found in waterfowls, we analyzed the internal organs of healthy ducks (Shaxoxing Sheldrake) from 1-day-old to 28-day-old raised in the natural environment. The dCATH mRNA expression level across tissues was determined via quantitative real-time polymerase chain reaction (qRT-PCR). Monoclonal antibody against the mature dCATH peptide used in enzyme-linked immunosorbent assay (ELISA) was prepared by the lymphocyte hybridoma technique for the first time. The concentration of the dCATH peptide in tissues was determined by ELISA. It showed that the dCATH mRNA had a clear tissue-specificity and age-dependent expression pattern, and it was highly expressed in the bone marrow and moderately expressed in the liver, kidney, spleen, pancreas and bursa of healthy duck. The peptide levels of dCATH in liver, kidney, spleen, pancreas and bursa changed with the age of duck, and the peptide concentration in these organs was between 88 and 128 ng/g tissue. For the first time, we characterized the concentration of the cHDP dCATH in vivo. Our study may represent new insights into the crosstalk of innate immunity, tissue development and age. [ABSTRACT FROM AUTHOR]

NZ2114 is a promising candidate for therapeutic application owing to its potent activity to Staphylococcus aureus. Our objective was to identify NZ2114 derivatives with improved activity through substitution of His16 and His18 with residues Arginine and Lysine. Eight mutants were designed and expressed in Pichia pastoris X-33 via pPICZαA. Five of them exhibited strong antimicrobial activity against S. aureus at low minimal inhibitory concentrations (MICs) of 0.057-0.454 μM. Among them, H1, H2, and H3 showed ideal pharmacodynamic effects on methicillin-resistant S. aureus ATCC43300. The total protein level of H1, H2, and H3 reached 1.70, 1.77 and 1.54 g/l at 120 h of induction in the 5-l fermenter, respectively. They killed over 99.9% of pathogens within 1.5 h at 2× and 4× MIC. The post antibiotic effect of H1, H2 and H3 to S. aureus ATCC43300 was 2.94, 1.75 and 1.55 h at 2× MIC, which was similar with their original peptide NZ2114 (1.43 h) and vancomycin (1.72 h). The fractional inhibitory concentration index (FICI) indicated indifferent effects between H1, H2, H3 and vancomycin, ampicillin, rifampicin. Additionally, they had low hemolysis and high stability in different environments (temperature, pH, proteases, and saline ions). All results indicate that H1, H2, and H3 can be produced in large-scale and have potential as therapeutic drugs against MRSA. [ABSTRACT FROM AUTHOR]

NZ2114 is a promising candidate for therapeutic application owing to potent activity to gram-positive bacterium such as Streptococcus pneumoniae and Staphylococcus aureus. This work is the first report to describe the in vitro and in vivo antibacterial characteristics of NZ2114 against Streptococcus suis. It exhibited strong antimicrobial activity against S. suis type 2 strains CVCC 606, CVCC 3309, and CVCC 3928 at a low minimal inhibitory concentration (MIC) of 0.03-0.06 μM. The NZ2114 killed over 99.9% of tested S. suis CVCC 606 in Mueller-Hinton medium within 4 h when treated with 4 × MIC. It caused only less than 0.25% hemolytic activity in the concentration of 256 μg/ml. Additionally, NZ2114 exhibited potent in vivo activity to S. suis. All mice were survival when the dosage was low to 0.2 mg/kg. Over 99% of S. suis cells were killed within 4 h in blood, lung, liver and spleen with dosage of 10, 20, and 40 mg/kg in mice peritonitis models and no pathogen were detected after 24 h of treatment. Further, no pathological phenomenon in lung and low level of inflammatory cytokines in blood were detected. These results indicate that NZ2114 has the potential to be a new antimicrobial agent candidate for the clinical treatment of infection caused by S. suis type 2. [ABSTRACT FROM AUTHOR]

Aflatoxins are produced as secondary metabolites by the toxigenic Aspergillus fungi. Among the aflatoxins, aflatoxin B1 (AFB1) is a common contaminant of global concern in human and animal food products. Prolonged exposure to AFB1 may provoke hepatocyte pyroptosis and oxidative stress, which leads to liver damage. Dietary polyphenols could protect the liver from a wide range of toxins. Curcumin, a polyphenolic substance derived from turmeric, is rich in pharmacological activity. The aim of this study was to systematically investigate the protective effects of curcumin against AFB1-induced liver injury in mice and to explore the possible molecular mechanisms. BALB/c mice received oral gavage of AFB1 (0.75 mg/kg) and curcumin (100 or 200 mg/kg) for 30 days. Our data demonstrated that curcumin attenuated AFB1-induced weight loss in mice and rescued liver injury by mitigating the alterations in pathology and liver function with AFB1 exposure. Curcumin reduced the accumulation of AFB1-DNA adducts in the liver and alleviated hepatotoxicity by inhibiting AFB1-induced oxidative stress and potentiating glutathione S-transferase (GST)-mediated phase II detoxification. In addition, curcumin significantly reduced the characteristic indices of AFB1-induced pyroptosis, such as the expression of mRNAs for genes related to NOD-like receptor protein 3 (NLRP3) inflammasome assembly and activation, the expression of key proteins (NLRP3, Caspase-1 and GSDMD). The release of interleukin-1β (IL-1β) and interleukin-18 (IL-18) in the serum detected by ELISA was also significantly decreased. Notably, administration of curcumin upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and its related downstream antioxidant molecules (SOD, CAT, HO-1, NQO1) and phase II detoxification enzyme-related molecules (GST, GSH, GSS, GCLC, GCLM) in the presence of AFB1 exposure. To summarize, our results indicated that curcumin could modulate the NLRP3 inflammasome and Nrf2 signaling pathways to attenuate AFB1-induced liver pyroptotic damage and oxidative stress. [ABSTRACT FROM AUTHOR]

Simple Summary: This study clarified for the first time that the Nrf2 and NF-κB signaling pathways in ducks are related to the antioxidant and anti-inflammatory effects. For the first time, we found that dietary resveratrol (RES) effectively alleviated the inflammatory response caused by lipopolysaccharide (LPS) by reducing oxidative stress and endoplasmic reticulum stress, alternating the blood biochemical index, and restoring the destruction of hepatocyte morphology. The results of this study provide strong evidence that dietary RES improved the anti-inflammatory ability and the growth performance of ducks. The aim of this study was to explore the effect of dietary resveratrol on the growth performance and anti-inflammatory mechanism in ducks. A total of 280 one-day-old specific pathogen-free male ducklings (Anas platyrhynchos) with an average body weight of 35 ± 1 g were randomly divided into two dietary treatment groups with different supplementation levels of resveratrol for growth performance experiments: R0 and R400 (0 and, 400 mg kg−1 resveratrol, respectively). At the age of 28 days, 16 ducks were selected from each treatment group and divided into four subgroups for a 2 × 2 factorial pathological experiment: R0; R400; R0 + LPS; R400 + LPS, (0 mg kg−1 resveratrol, 400 mg kg−1 resveratrol, 0 mg kg−1 resveratrol, 400 mg kg−1 resveratrol + 5 mg lipopolysaccharide/kg body weight). The results showed that resveratrol significantly improved final body weight and average daily gain (p < 0.01) and alleviated the lipopolysaccharide-induced inflammatory response with a reduction in IL-1β and IL-6 in the plasma and the liver (p < 0.05). Resveratrol improved mRNA levels of Nrf2 and HO-1 and decreased the mRNA levels of TLR4 and NF-κB in duck liver (p < 0.05). Dietary resveratrol can improve growth performance and reduce inflammation through the Nrf2/HO-1 and TLR4/NF-κB signaling pathways in duck. [ABSTRACT FROM AUTHOR]

Simple Summary: Aflatoxin B1 is ubiquitous in food and feed, which not only poses a great threat to animals, but also affects human health. It is unclear whether resveratrol can resist aflatoxin B1 damage in ducks' livers. Therefore, the effect of resveratrol supplementation in the diets on liver injury aflatoxin B1was investigated through the gavage of aflatoxin B1. It was found that a diet that includes resveratrol can effectively protect ducks' livers from acute injury caused by aflatoxin B1. Our study suggests that resveratrol serves as a potential phytochemical feed additive for the treatment of acute aflatoxin B1 poisoning in ducks The presence of aflatoxin B1 (AFB1) in feed is a serious threat to livestock and poultry health and to human food safety. Resveratrol (Res) is a polyphenolic compound with antioxidant, anti-apoptotic and other biological activities; however, it is not clear whether it can improve AFB1 induced hepatotoxicity. Therefore, this study was conducted to investigate the effects of dietary Res on liver injury induced by AFB1 and its mechanisms. A total of 270 one-day-old male specific pathogen free (SPF) ducks, with no significant difference in weight, were randomly assigned to three groups: the control group, the AFB1 group and the AFB1 + Res group, which were fed a basic diet, a basic diet and a basic diet containing 500 mg/kg Res, respectively. On the 70th day, the ducks in theAFB1 group and the AFB1+ 500 mg/kg Res group were given 60 μg/kg AFB1 via gavage. When comparing the AFB1 group and the AFB1 + Res group and also with the control group, AFB1 significantly increased liver damage, cytochrome P450 (CYP450) and AFB1-DNA adduct content, increased oxidative stress levels and induced liver apoptosis, which was improved by Res supplementation. In sum, the addition of Res to feed can increase the activity of the II-phase enzyme, activate the nuclear factor E2-related factor 2 (Nrf2) signal pathway, and protect ducks' livers from the toxicity, oxidative stress and inflammatory reaction induced by AFB1. [ABSTRACT FROM AUTHOR]

The family of antimicrobial peptide, cathelicidins, which plays important roles against infections in animals, has been identified from many species. Here, we identified a novel avian cathelicidin ortholog from ducks and named dCATH. The cDNA sequence of dCATH encodes a predicted 146-amino-acid polypeptide composed of a 17-residue signal peptide, a 109-residue conserved cathelin domain and a 20-residue mature peptide. Phylogenetic analysis demonstrated that dCATH is highly divergent from other avian peptides. The α-helical structure of the peptide exerted strong antimicrobial activity against a broad range of bacteria in vitro, with most minimum inhibitory concentrations in the range of 2 to 4 μM. Moreover, dCATH also showed cytotoxicity, lysing 50% of mammalian erythrocytes in the presence or absence of 10% fetal calf serum at concentrations of 32 μM or 20 μM and killing 50% HaCaT cells at a concentration of 10 μM. The effects on bacterial outer and inner membranes, as examined by scanning electron microscope and transmission electron microscopy, indicate that dCATH kills microbial cells by increasing permeability, causing a loss of membrane integrity. [ABSTRACT FROM AUTHOR]