Assessment of the anti-inflammatory mechanism of quercetin 3,7-dirhamnoside using an integrated pharmacology strategy.

Pouzolzia zeylanica (L.) Benn. is a Chinese herbal medicine widely used for its anti-inflammatory and pus-removal properties. To explore its potential anti-inflammatory mechanism, quercetin 3,7-dirhamnoside (QDR), the main flavonoid component of P. zeylanica (L.) Benn., was extracted and purified. The potential anti-inflammatory targets of QDR were predicted using network analysis. These potential targets were verified using molecular docking, molecular dynamics simulations, and in vitro experiments. Consequently, 342 potential anti-inflammatory QDR targets were identified. By analyzing the intersection between the protein-protein interaction and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, we identified several potential protein targets of QDR, including RAC-alpha serine/threonine-protein kinase (AKT1), Ras-related C3 botulinum toxin substrate 1 (RAC1), nitric oxide synthase 3 (NOS3), serine/threonine-protein kinase mTOR (mTOR), epidermal growth factor receptor (EGFR), growth factor receptor-bound protein 2 (GRB2), and endothelin-1 receptor (EDNRA). QDR has anti-inflammatory activity and regulates immune responses and apoptosis through chemokines, Phosphatidylinositol 3-kinase 3(PI3K)/AKT, cAMP, T-cell receptor, and Ras signaling pathways. Molecular docking analysis showed that QDR has good binding abilities with AKT1, mTOR, and NOS3. In addition, molecular dynamics simulations demonstrated that the protein-ligand complex systems formed between QDR and AKT1, mTOR, and NOS3 have high dynamic stability, and their protein-ligand complex systems possess strong binding ability. In RAW264.7 macrophages, QDR significantly inhibited lipopolysaccharides (LPS)-induced inducible nitric oxide synthase expression, nitric oxide (NO) release and the generation of proinflammatory cytokines IL-6, IL-1ß, and TNF-α. QDR downregulated the expression of p-AKT1(Ser473)/AKT1 and p-mTOR (Ser2448)/mTOR, and upregulated the expression of NOS3, Rictor, and Raptor. This indicates that the anti-inflammatory mechanisms of QDR involve regulation of AKT1 and mTOR to prevent apoptosis and of NOS3 which leads to the release of endothelial NO. Thus, our study elucidated the potential anti-inflammatory mechanism of QDR, the main flavonoid found in P. zeylanica (L.) Benn.

Zinc and COVID-19: Immunity, Susceptibility, Severity and Intervention.

During the coronavirus disease 2019 (COVID-19) pandemic and continuing emergence of viral mutants, there has been a lack of effective treatment methods. Zinc maintains immune function, with direct and indirect antiviral activities. Zinc nutritional status is a critical factor in antiviral immune responses. Importantly, COVID-19 and zinc deficiency overlap in high-risk population. Hence, the potential effect of zinc as a preventive and adjunct therapy for COVID-19 is intriguing. Here, this review summarizes the immune and antiviral function of zinc, the relationship between zinc levels, susceptibility, and severity of COVID-19, and the effect of zinc supplementation on COVID-19. Existing studies have confirmed that zinc deficiency was associated with COVID-19 susceptibility and severity. Zinc supplementation plays a potentially protective role in enhancing immunity, decreasing susceptibility, shortening illness duration, and reducing the severity of COVID-19. We recommend that zinc levels should be monitored, particularly in COVID-19 patients, and zinc as a preventive and adjunct therapy for COVID-19 should be considered for groups at risk of zinc deficiency to reduce susceptibility and disease severity.

Integrated multi-omics uncovers reliable potential biomarkers and adverse effects of zinc deficiency.

BACKGROUND: Zinc deficiency is a worldwide public health problem. Currently, there are no established biomarkers available for the accurate diagnosis of zinc-deficiency in individuals. Additionally, a comprehensive view of the adverse effects of zinc deficiency is lacking. Our aim was to identify superior biomarkers of zinc deficiency and uncover the adverse effects of zinc deficiency. METHODS: We performed multi-omics analysis using serum proteomics-metabolomics and liver proteomics on zinc-deficient rats to identify candidate biomarkers and reveal the associated adverse effects of zinc deficiency. Secondly, the candidate biomarkers were validated in two zinc-deficient populations and an RCT zinc supplementation trial on a zinc-deficient population. RESULTS: Our integrated multi-omics approach revealed numerous biomarkers (>2000) and glutathione metabolism as the most important changed pathway in zinc deficiency. Three candidate biomarkers from glutathione metabolism were validated in repeated zinc-deficient rats by quantitative analysis. Only glutathione sulfotransferase omega-1 (GSTO1) (among 3 candidate biomarkers) was validated in the two zinc-deficient populations and zinc-supplemented population. Compared with serum zinc, serum GSTO1 yielded a better response to zinc supplementation and a higher correlation coefficient with zinc intake and the AUC value and has the potential for diagnosing zinc deficiency. By integrated multi-omics, we identified both established and novel adverse effects of zinc deficiency. CONCLUSIONS: Our integrated multi-omics analysis revealed more complete information about zinc deficiency; GSTO1 was found to be a reliable potential biomarker for diagnosis of zinc deficiency. This trial is registered at http://www.chictr.org.cn/registry.aspx as ChiCTR1900028162.

Discrimination of heating and frying vegetable oils based on UPLC/Q-TOF MSMS and chemometrics.

Fried foods have potential adverse effects on health. However, the compounds produced during the process of frying in different vegetable oils are unknown. In this work, ultra performance liquid chromatography (UPLC), quadrupole time-of-flight mass spectrometry (Q-TOF MSMS) and chemical pattern recognition analysis was first conducted to analyze the changes in compounds in 8 different vegetable oils before and after thin-layer heating (without food) and to reveal the potential markers of oil used for deep-frying food. Then, these markers were validated in used frying oil. Our results of principal component analysis (PCA), partial least-squares discriminant analysis (PLS-DA) indicated that both thin-layer heating and deep-frying significantly change the compounds of vegetable oils. Thirty-six of the markers associated with thin-layer heating from the 8 different oils were identified in used frying oils and can be used as common markers of oil used for deep-frying. Additionally, 22 markers detected in individual vegetable oils provided unique markers of used frying oils. These markers can be used to distinguish used frying oil and have the potential to reveal the associated physiological harm.

Assessment of the efficacy of using taurine supplements to improve growth and feed utilization of juvenile starry flounder (Platichthys stellatus) given diets based on soy-protein.

A feeding trial was conducted to assess the feasibility of supplementing taurine in soy-based diets for juvenile starry flounder Platichthys stellatus. The basal diet (Crude protein 66.5%, crude lipid 8.5%) was supplemented with 0 (control), 0.5%, 1.0%, 1.5%, 2.0% and 2.5% taurine to formulate six test diets. Each diet was fed to 40 juvenile fish (22.25 g) in triplicate tanks (120 L) attached to a sea water circulation-system. Fish were fed twice daily by hand to apparent satiation during the 56-d trial. At the end of the trial, fish were counted and weighed for the analyses of growth performance, diet utilization and survival after a 24-h fast. Blood, intestines and muscles were collected for the analyses of serum oxidation resistance, digestive enzymes and body compostion. Livers were collected from the remaining fish at 4 h post-feeding for metabolic enzymes analyses. The results showed that fish fed diets supplemented with 1.0-2.5% taurine grew from 22.25-22.26 g to 47.88-50.40 g with higher average weight gain (25.62-28.12 vs 23.07 g ), specific growth rate (1.37-1.46 vs 1.27%/d ), feed intake (1.04-1.06 vs 1.00%/d), protein efficiency (2.50-2.61 vs 2.44) and lower feed conversion rate (0.84-0.83 vs 0.89) than the control treatment. Diets supplemented with 1.5-2.5% taurine significantly elevated the activities of pepsin (2.47-2.55 vs 2.22, U mg-1 prot), trypsin of distal intestine(14.55-15.24 vs 11.94, U mg-1 prot), hepatic glucokinase (126.62-129.42 vs 105.56, U mg-1 prot) and fatty acid synthetase (125.56-136.89 vs 108.45, U mg-1 prot). All diets supplemented with taurine increased the activities of lipase (32.23-36.67 vs 29.53, U g-1 prot) and trypsin (35.85-37.89 vs 33.54, U mg-1 prot) of proximal intestine, hepatic aspartate transaminase (736.990-832.38 vs 699.24, U mg-1 prot), alanine aminotransferase (477.40-551.86 vs 373.97, U mg-1 prot) and glycogen synthase (2.16-2.59 vs 1.97, U mg-1 prot), as well as serum superoxide dismutase (4.33-4.59 vs 4.07, U mg-1 prot ) and glutathione peroxidase (42.23-50.25 vs 39.17, mol mg-1 prot). Therefore, taurine supplementation benefits juvenile starry flounder growth, digestion, nutrients metabolism and oxidation resistance. The optimal taurine requirement for starry flounder is 1.75%, and the recommended supplementation level is at least 1.6% for maximizing growth of fish fed a low-fishmeal diet (13.6%).

The effects of zinc deficiency on homeostasis of twelve minerals and trace elements in the serum, feces, urine and liver of rats.

BACKGROUND: Zinc deficiency can change the concentrations of minerals and trace elements in the body. However, previous studies still had many limitations. OBJECTIVE: To reveal the effects of zinc deficiency on homeostasis of 16 minerals and trace elements. METHODS: Forty-five rats were divided randomly into three groups: normal zinc diet (30 mg/kg), low zinc diet (10 mg/kg), and pair-fed diet(30 mg/kg). The concentrations of 16 minerals and trace elements in serum, feces, urine, and liver were measured by inductively coupled plasma mass spectrometry. The excretion of 16 elements in urine and feces were calculated and compared. RESULTS: Zinc-deficient rats exhibited significant changes in up to 12 minerals and trace elements. The low zinc diet induced decreased excretion of zinc and concentrations of zinc in serum, feces, urine, and liver. Zinc deficiency increased feces concentrations of Mg, Cu, Se, K, Ag, Fe and Mn; decreased the concentrations of Mg, Cu, Se, K in liver and urine, and a diminished amount of Ag was observed in serum. Decreased urinary concentrations of Zn Ca, Mg, Cu, Se, K, Na, As and Cr, suggested that zinc-deficient rats increased the 9 elements' renal reabsorption. Decreased concentrations of Ca in liver, urine, and feces, decreased excretion in urine and feces and increased serum total Ca suggested that zinc deficiency increased the redistribution of Ca in serum or other tissues. Zinc deficiency increased excretion of Cu, Se, Fe; and decreased the excretion of other 8 elements except for Ag. CONCLUSIONS: Zinc deficiency changed the excretion, reabsorption and redistribution of 12 minerals and trace elements in rats. Our findings are the first to show that zinc deficiency alters the concentrations of Ag, Cr, and As. SUPPLEMENTARY INFORMATION: Supplementary information accompanies this paper at 10.1186/s12986-019-0395-y.