Flavonoids are important dietary phytochemicals with broad human exposures and a variety of claimed biological effects. Although traditional sources of flavonoids are fruits and vegetables, dietary supplements have become an important source of flavonoids. The enthusiasm for all things about flavonoids expressed by scientists and public alike has sometimes overlooked an important point: these compounds are usually not bioavailable or have very low bioavailability. The current review focused on factors that affect bioavailability of flavonoids, which in turn impact their efficacy and toxicity. These factors include physicochemical and biological ones, with the emphasis on the latter, including membrane permeation, enzymatic metabolism, and excretion by efflux transporters. Current evidence indicates that naturally occurring flavonoid glycosides typically need to be de-glycosylated before they are absorbed, because intact flavonoid glycosides are poorly absorbed. However, once absorbed, flavonoid aglycones undergo rapid and extensive first-pass metabolism via conjugation and subsequent excretion of the conjugates, which makes them poorly bioavailable. Fortunately, the presence of enteric and enterohepatic recycling allows the flavonoids to be accumulated in vivo over time, because the recycling increases contact time between the flavonoids and target tissues. We believe that continued studies in this area will help scientists devise a better means to improve oral bioavailability of flavonoids so we can one day fully enjoy the health benefits of ingesting flavonoids.
Background: Huashi Baidu Formula (HSBDF) is a traditional Chinese medicine formula consisting of fourteen parts, which has been proven effective for treating coronavirus disease 2019 (COVID-19) clinically.However, the therapeutic mechanism of the effect of HSBDF on COVID-19 remains unclear.Methods: The components and action targets of HSBDF were searched in the TCMSP, YaTCM, PubChem, and TargetNet databases. Disease targets related to ACE2 were screened in single-cell sequence data of colon epithelial cells from other reports. The therapeutic targets of HSBDF for COVID-19 were obtained by integrated analysis, and the protein-protein interaction was analyzed using the STRING database. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) processes were analyzed using the OmicsBean and Metascape databases. The communication between networks [component-target (C-T) network, component-target-pathway (C-T-P) network, herb-target (H-T) network, target-pathway (T-P) network, and meridian-tropism (M-T) network] was constructed by Cytoscape software. The Cloud computing molecular docking platform was used to verify the molecular docking.Results: The obtained 223 active ingredients and 358 targets of HSBDF. The 5,555 COVID-19 disease targets related to ACE2 were extracted, and 84 compound-disease common targets were found, of which the principal targets included ACE, ESR1, ADRA1A, and HDAC1. A total of 3,946 items were seized by GO enrichment analysis, mainly related to metabolism, protein binding, cellular response to the stimulus, and receptor activity. The enriched KEGG pathways screened 46 signaling pathways, including the reninangiotensin system, the renin secretion, NF-kappa B pathway, the arachidonic acid metabolism, and the AMPK signaling pathway. The molecular docking results showed that the bioactive components of HSBDF have an excellent binding ability with main proteins related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).Conclusions: HSBDF might act on SARS-CoV-2 through multiple components, targets, and pathways.Here we reveal preliminary results of the mechanism of action of HSBDF on SARS-CoV-2, providing a theoretical basis for future clinical applications.
Background: Human enabled homolog (ENAH; also known as human ortholog of mammalian enabled, hMENA) is a member of the enabled/vasodilator-stimulated phosphor protein family that regulates fibroblast movement and nervous system development. The ENAH over-expression promotes breast cancer (BC) cell invasion and metastasis. Methods: We studied ENAH mRNA expression in various tumors and normal tissues using the ONCOMINE database, and in an array of cancer cell lines using Cancer Cell Line Encyclopedia data. We also investigated the prognostic value of ENAH expression in patients with BC using Kaplan-Meier plots. Results: Compared with normal tissues, ENAH expression levels were markedly elevated in BC. We identified a correlation between low ENAH and superior relapse-free survival (RFS) of patients with BC; specifically, those with ER(-), HER-2(+), Grade 3 and wild-type TP53 subtypes. Additionally, a correlation was detected between low ENAH and prolonged overall survival of patients with luminal B disease. Conclusion: ENAH is a potential biomarker and important prognostic factor in BC.
Introduction: Cesarean scar defect (CSD) is a long-term outcome of cesarean section (CS) and associated with numerous gynecological and obstetric problems. Previous studies indicate that infection may be a risk factor for CSD. Adjunctive azithromycin was shown to reduce the risk of postoperative infection in patients undergoing non-elective primary cesarean delivery in labor or after the rupture of membranes compared with standard antibiotic prophylaxis. This study investigated the protective effect of adjunctive azithromycin in combination with single-dose cephalosporin against CSD in women undergoing non-elective cesarean delivery. Material and methods:A randomized, double-blind, controlled clinical trial was conducted in a University hospital in Shanghai, China. A total of 242 women who underwent their first non-elective CS were randomly assigned to receive 1500 mg cefuroxime sodium plus 500 mg intravenous azithromycin (n = 121; experimental group) or 1500 mg cefuroxime sodium plus a placebo (n = 121; placebo group). The primary outcome was CSD prevalence, as determined by transvaginal ultrasound and saline infusion sonohysterography within 6 months of delivery. Secondary outcomes were changes in infectious indicators (eg hypersensitive C-reactive protein and procalcitonin), postoperative morbidity, and use of postoperative antibiotics. We also examined the operative procedure, pathogenic microorganism cultures, and fetal outcomes. Outcomes were compared between groups with the chi-squared test, Fisher's exact test, or Student's t test.Results: Between May 2018 and May 2021, 121 women were randomized to each arm. Because the sonographic follow up was disrupted by the coronavirus disease 2019 pandemic and strict management policies, we merged the follow-up time points (6 weeks and 6 months) into a single time period (6 weeks to 6 months); 104 and 108 women in the experimental and placebo groups, respectively, completed the first sonographic follow up. CSD was diagnosed by sonography in 34/104 (32.7%) and
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