RESUMO
Engineered probiotics can serve as therapeutics based on their ability of produce recombinant immune-stimulating properties. In this study, we built the recombinant Bacillus subtilis WB800 expressing antimicrobial peptide KR32 (WB800-KR32) using genetic engineering methods and investigated its protective effects of nuclear factor-E2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) pathway activation in intestinal oxidative disturbance induced by enterotoxigenic Escherichia coli (ETEC) K88 in weaned piglets. Twenty-eight weaned piglets were randomly distributed into four treatment groups with seven replicates fed with a basal diet. The feed of the control group (CON) was infused with normal sterilized saline; meanwhile, the ETEC, ETEC+WB800, and ETEC+WB800-KR32 groups were orally administered normal sterilized saline, 5×1010 CFU (CFU: colony forming units) WB800, and 5×1010 CFU WB800-KR32, respectively, on Days 1‒14 and all infused with ETEC K88 1×1010 CFU on Days 15‒17. The results showed that pretreatment with WB800-KR32 attenuated ETEC-induced intestinal disturbance, improved the mucosal activity of antioxidant enzyme (catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx)) and decreased the content of malondialdehyde (MDA). More importantly, WB800-KR32 downregulated genes involved in antioxidant defense (GPx and SOD1). Interestingly, WB800-KR32 upregulated the protein expression of Nrf2 and downregulated the protein expression of Keap1 in the ileum. WB800-KR32 markedly changed the richness estimators (Ace and Chao) of gut microbiota and increased the abundance of Eubacterium_rectale_ATCC_33656 in the feces. The results suggested that WB800-KR32 may alleviate ETEC-induced intestinal oxidative injury through the Nrf2-Keap1 pathway, providing a new perspective for WB800-KR32 as potential therapeutics to regulate intestinal oxidative disturbance in ETEC K88 infection.
Assuntos
Animais , Suínos , Escherichia coli Enterotoxigênica , Proteína 1 Associada a ECH Semelhante a Kelch , Bacillus subtilis , Fator 2 Relacionado a NF-E2 , Antioxidantes , Estresse OxidativoRESUMO
Anti-D immunoglobulin effectively prevents RhD alloimmunity and has a low incidence of adverse reactions, which are generally mild. A consensus is yet to be reached regarding the clinical norms in China. We provide an overview of anti-D immunoglobulin in preventing RhD alloimmunity, including its mechanism of action, dose-effect, and safety, the timing and rationality of prenatal antibody screening, the timing and dosage of routine prenatal administration of anti-D immunoglobulin, as well as the prenatal indications for an additional dosage of anti-D immunoglobulin and postpartum prevention based on evidence from both domestic and abroad.
RESUMO
Objective:To explore concordance between preoperative core needle biopsy(CNB)and resection specimen(RS)in evaluat-ing biomarkers and molecular subtypes with immunohistochemical method.Methods:A retrospective study was performed on 324 breast cancer patients who underwent modified radical mastectomy at the Tianjin Medical University Cancer Institute and Hospital be-tween August 2015 and November 2016.All patients who had received neoadjuvant systemic therapy were excluded.The aim of this analysis was to report concordance between CNB and surgical specimens in evaluating biomarkers,such as ER,PR HER-2,Ki-67,and molecular subtypes.Results:There was concordance between estrogen receptor(ER)assessment on CNB and RS in 94.1%(305/324) of the patients(κ=0.84).Concordance of the progesterone receptor(PR)and the human epidermal growth factor receptor 2(HER-2) assessments were observed in 90.7%(294/324,κ=0.76)and 61.1%(198/324,κ=0.38)patients,respectively.Evaluation of Ki-67 re-vealed an accordance rate of 86.7%(281/324,κ=0.34),and the concordance for immunohistochemistry detection for assessing breast cancer(BC)molecular subtypes was 73.4%(91/124,κ=0.64).Conclusions:Although CNB showed good accuracy for evaluating hormon-al receptor status and BC molecular subtypes,its evaluation of HER-2 and Ki-67 statuses was less accurate than other biomarkers. Therefore,we should combine immunohistochemical results with both CNB and RS samples in order to improve accuracy when diag-nosing molecular subtypes.Moreover,improved diagnoses can provide the basis for more effective systemic therapies.