UPLC-QTOF-MS-based lipidomic study of wedelolactone in acute colitis mice induced by dextran sulfate sodium.

Inflammatory bowel disease is a relapsing inflammatory disease seriously endanger human health. Wedelolactone (WED) is a major active ingredient from Eclipta prostrata (L.) L. and has shown anti-inflammatory effects. However, the mechanism of WED in treating inflammatory colitis remains unknown. We aimed to investigate the mechanisms of WED in treating ulcerative colitis through lipidomic study. Sixty male C57BL/6 mice were exposed to DSS to induce acute colitis. Disease progression was judged by the disease activity index (DAI) and pathological changes of colon tissue. An ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) method was performed for colon and plasma lipidomics analyses. Differential metabolites in the three groups were distinguished by univariate and multivariate analysis. WED exerted anti-inflammatory effects representing by body weight and DAI score. Three metabolites were identified in plasma and 20 in colon. According to pathway analysis, the effects of WED on colitis were associated with seven pathways. The glycerophospholipid metabolism and ether lipid metabolism were the primary pathways. The findings provide important insight of the mechanism of WED in treating DSS induced colitis through lipidomic perspective.

Changes in coagulation indices and D-dimer levels in hypertriglyceridemic acute pancreatitis and their value in predicting disease severity. / é«˜ç”˜æ²¹ä¸‰é ¯è¡€ç—‡æ€§æ€¥æ€§èƒ°è ºç‚Žå‡è¡€æŒ‡æ ‡ä¸ŽD-äºŒèšä½“æ°´å¹³å˜åŒ–åŠå ¶é¢„æµ‹ç–¾ç— ä¸¥é‡ç¨‹åº¦çš„ä»·å€¼.

OBJECTIVES: Hypertriglyceridemic acute pancreatitis (HTG-AP) is one of the common acute and severe cases of digestive system. Incidence of HTG-AP is increasing year by year, and there is a trend of younger and severe cases. Early identification of severe patients and timely intervention are conducive to improve the prognosis. Dysfunction of coagulation and fibrinolysis systems plays an important role in the development of HTG-AP. Prothrombin time (PT) and activated partial thromboplastin time (APTT) are sensitive indicators of exogenous and endogenous coagulation system, respectively. Fibrinogen (FIB) is an acute reactive protein with coagulation function. D-dimer is a sensitive index to judge the abnormality of coagulation and fibrinolysis system. This study aims to investigate the changes of coagulation parameters and D-dimer level in patients with HTG-AP and their value in predicting the severity of the disease. METHODS: The clinical data of 189 HTG-AP patients admitted to Jiangjin Hospital Affiliated to Chongqing University (Jiangjin District Central Hospital of Chongqing) from January 2019 to December 2020 were collected, including gender, age, medical history, complications, causes, and acute physiology and chronic health evaluation II (APACHE II) scores. According to the severity of the disease, the patients were divided into a mild HTG-AP group and a severe HTG-AP group. The changes of coagulation indexes (PT, APTT and FIB), D-dimer and C-reactive protein (CRP) levels were detected. Coagulation indexes, D-dimer level and disease severity (CRP level, APACHE II scores) were compared between the 2 groups. Spearman correlation analysis was used to analyze the correlation between the above indexes. Univariate and multivariate binary logistic regression analysis were used to identify the independent risk factors for severe HTG-AP. Receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to analyze the predictive value of PT, FIB, and D-dimer for the severity of HTG-AP. RESULTS: There were significant differences in gender between the mild HTG-AP group and the severe HTG-AP group (P<0.05). There was no significant difference in age, recurrence rate and incidence of complications between the 2 groups (all P>0.05). The basic conditions of the 2 groups were similar and comparable. PT, FIB and D-dimer levels in the severe HTG-AP group were significantly higher than those in the mild HTG-AP group (all P<0.001). There was no significant difference in APTT between the 2 groups (P>0.05). The CRP level and APACHE II scores in the severe HTG-AP group were significantly higher than those in the mild HTG-AP group (all P<0.05). Spearman correlation analysis showed that PT, FIB and D-dimer were positively correlated with CRP and APACHE II scores (all P<0.05), while APTT was not correlated with CRP and APACHE II scores (all P>0.05). Logistic regression analysis showed that prolonged PT and elevated D-dimer level were independent risk factors for severe HTG-AP (both P<0.05). ROC curve analysis showed that the AUC of PT for predicting severe HTG-AP was 0.764 (95% CI 0.690 to 0.837, P<0.001), when PT>14.40 s, the sensitivity, specificity, positive predictive value, and negative predictive value were 63.07%, 79.03%, 59.42%, and 80.00%, respectively. TheAUC of FIB for predicting severe HTG-AP was 0.669 (95% CI 0.588 to 0.751, P<0.001), when FIB>4.18 g/L, the sensitivity, specificity, positive predictive value, and negative predictive value were 61.53%, 70.17%, 49.38%, and 76.85%, respectively. The AUC of D-dimer for predicting severe HTG-AP was 0.753 (95% CI 0.680 to 0.826, P<0.001), when D-dimer>1.28 µg/mL, the sensitivity, specificity, positive predictive value, and negative predictive value were 73.84%, 66.12%, 53.33%, and 82.82%, respectively. The AUC of PT combined with D-dimer for predicting severe HTG-AP was 0.797. CONCLUSIONS: There are abnormalities in coagulation and fibrinolytic system in patients with HTG-AP in the early stage. PT, FIB and D-dimer levels are increased with the aggravation of the AP, and have a positively correlation with it. Elevated PT and D-dimer level are independent risk factors for severe HTG-AP. PT combined with D-dimer may be a sensitive indicator for prediction of the severity of HTG-AP in early phase.

Lipidomics Study of Sepsis-Induced Liver and Lung Injury under Anti-HMGB1 Intervention.

Sepsis usually leads to lethal multiorgan dysfunction including acute liver failure (ALF) and acute lung injury (ALI). This research sought to reveal the lipid alteration of anti-high mobility group box 1 (HMGB1) treatment in sepsis-induced ALF and ALI by lipidomics. The cecal ligation and puncture-induced mouse model was established and the anti-HMGB1 neutralizing antibody was administrated. The histopathological characteristics and inflammatory factors were determined to assess the efficacy of the antibody. Utraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was used to determine lipid metabolism profiles in the liver and lung. The underlying biomarkers were identified through multivariate statistical analysis and correlation analysis with traditional physiological indicators. The pathological and biochemical results demonstrated that anti-HMGB1 neutralizing antibodies mitigated ALF and ALI in mice. Three differential metabolites in the liver and six various metabolites in the lung were significantly reversed by anti-HMGB1 treatment, mainly involved in arachidonic acid metabolism, glycerophospholipid metabolism, and sphingolipid metabolism. Additionally, we investigated several traditional signaling pathways associated with HMGB1. However, the correlation between these traditional pathways and anti-HMGB1 intervention was not significant in the current study. In conclusion, our finding provided some scientific basis for targeting HMGB1 in sepsis-induced liver and lung injury. Mass spectrometry data with identifier no. MTBLS6466 have been uploaded to MetaboLights (http://www.ebi.ac.uk/metabolights/login).

Revealing the biotoxicity of phosphorene oxide nanosheets based on the villin headpiece.

Phosphorene, a novel member of the two-dimensional nanomaterial family, has demonstrated great potential in biomedical applications, such as photothermal therapy, drug delivery and antibacterial. However, phosphorene is unstable and easily oxidized in an aerobic environment. In this paper, using larger-scale molecular dynamics simulations, we investigated the disruption of phosphorene oxide (PO) to the structure of a model protein, villin headpiece subdomain (HP35). It shows that the disruption of PO nanosheets to the protein structure is enhanced with increasing oxidation concentration of PO, while PO's oxidation mode has very little effect on the PO-HP35 interaction. PO with a low oxidation concentration has certain biocompatibility to HP35. Oxygen atoms filling into the groove region in the puckered surface of phosphorene enhance the dispersion interaction between phosphorene and HP35, which enhances the disruption of phosphorene to the structure of HP35. Compared with the dispersion interaction, the electrostatic interaction between PO and the protein has a negligible effect on the structural damage of HP35. These findings might shed light on the biological toxicity of PO nanosheets and would be helpful for future potential biomedical applications of PO nanosheets, such as nanodrugs and antibacterial agents.

The combination of pre-neoadjuvant chemoradiotherapy inflammation biomarkers could be a prognostic marker for rectal cancer patients.

The neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR) have a strong association with prognosis in patients with Stage II/III rectal cancer (RC). We attempted to explore a new system combining these two ratios, named the NLM score, and examine its prognostic value in Stage II/III RC patients undergoing neoadjuvant chemoradiotherapy (NCRT). We retrospectively analyzed data of 237 stage II/III RC patients who underwent NCRT followed by standard TME in our hospital and defined the NLM score as follows: Score 2: pre-NCRT NLR > 2.565 and pre-NCRT LMR < 2.410. Score 1: (pre-NCRT NLR > 2.565 and pre-NCRT LMR > 2.410) OR (pre-NCRT NLR < 2.565 and pre-NCRT LMR < 2.410). Score 0: pre-NCRT NLR < 2.565 and pre-NCRT LMR > 2.410. Multivariate analyses implied that lower ypTNM stage (stage 0-I vs. II-III) (hazard ratio [HR] 0.420, 95% confidence interval [CI] 0.180-0.980 for OS; HR 0.375, 95% CI 0.163-0.862 for DFS) and an NLM score ≤ 1 (HR 0.288, 95% CI 0.134-0.619 for OS; HR 0.229, 95% CI 0.107-0.494 for DFS) could independently predict better overall survival (OS) and disease-free survival (DFS). The novel scoring system, which integrated pre-NCRT NLR and pre-NCRT LMR, was an independent prognostic factor in stage II/III RC patients undergoing NRCT and had better predictive values than these ratios alone.

Comparative study of the effects of selenium yeast and sodium selenite on selenium content and nutrient quality in broccoli florets (Brassica oleracea L. var. italica).

BACKGROUND: Approximately 0.5-1 billion people worldwide face the risk of selenium (Se) deficiency because of the low Se concentration in their diets. Broccoli can accumulate Se and comprises a source of daily Se supplement for humans. Se biofortification is an effective strategy for enhancing Se content in crops. In the present study, the effects of Se yeast and selenite application on the Se content and nutrient quality of broccoli were investigated. RESULTS: Broccoli growth was promoted by Se yeast but inhibited by selenite. The total Se content of broccoli florets remarkably increased with increasing exogenous Se fertilizer concentrations. The main Se species in broccoli florets were methyl-selenocysteine and selenomethionine, and their contents were significantly higher under Se yeast treatments than under selenite treatments. Se(VI) was detected only under selenite treatments. Se yeast and selenite had different influences on soluble sugar, soluble protein, vitamin C and free amino acid contents in broccoli florets. The total phenolic acid and glucosinolate contents were substantially increased by Se yeast and selenite, although the total flavonoid content was reduced by Se yeast. Tests on antioxidant enzyme activities revealed that several antioxidant enzymes (catalase, peroxidase, superoxide dismutase and glutathione peroxidase) responded to Se yeast and selenite treatments. CONCLUSION: Se yeast is preferred over selenite for maximizing Se uptake and nutrient accumulation in Se-rich broccoli cultivation. However, an extremely high Se content in broccoli florets cannot be directly consumed by humans, although they can be processed into Se supplements. © 2021 Society of Chemical Industry.

UPLC-QTOF-MS Based Comparison of Rotundic Acid Metabolic Profiles in Normal and NAFLD Rats.

Rotundic acid, the principal bioactive constituent of the herbal remedy "Jiubiying", has been considered as a candidate compound for treating non-alcoholic fatty liver disease (NAFLD). However, the in vivo and in vitro metabolism of rotundic acid has remained unclear. With the aim of elucidating its metabolic profile, a reliable approach that used ultra-high performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) was applied for screening and identifying rotundic acid in vivo (plasma, feces, urine, and liver tissue of normal and NAFLD model rats) and in vitro (rat liver microsomes) metabolites. Herein, 26 metabolites of rotundic acid were identified, including 22 metabolites in normal rats, 20 metabolites in NAFLD model rats, and eight metabolites in rat liver microsomes. Among them, 17 metabolites were identified for the first time. These data illustrate that the pathological status of NAFLD affects the metabolism of rotundic acid. Furthermore, the major pathways of metabolism included phase Ⅰ (demethylation, desaturation, etc.) and phase Ⅱ (sulfation and glucuronidation) reactions, as well as a combined multiple-step metabolism. This work provides important information on the metabolism of rotundic acid and lays the foundation for its future clinical application.

Effects of selenate on Se, flavonoid, and glucosinolate in broccoli florets by combined transcriptome and metabolome analyses.

Broccoli is a nutritious vegetable popular all over the world. This study investigated the effects of different concentrations of selenate (0, 0.1, 0.2, 0.4, 0.8, and 1.6 mmol/L) on the selenium (Se), glucosinolate, and flavonoid contents of broccoli florets. Results showed that the total Se, selenomethionine, and methyl selenocysteine contents increased following selenate dosage. Interestingly, selenate treatment of 0.4 mmol/L decreased the flavonoid but increased the glucosinolate content. Metabolome analysis revealed changes in the individual contents of glucosinolates and flavonoids. Conjoint analysis of transcriptome and metabolome showed that the glucosinolate and flavonoid compounds were potentially regulated by two sulfate transporter genes (Sultr3;1 and Sultr4;2) and several cytochrome P450 genes (e.g., CYP71B21, CYP72C1, and CYP81F1). These new findings indicated that Se treatment may influence glucosinolate and flavonoid accumulation by regulating the expression of these genes. The results of this study provide some novel insights into the effects of Se on glucosinolates and flavonoids in broccoli florets and deepen our understanding of the regulatory network between some specific genes and these compounds.

Selenium yeast promoted the Se accumulation, nutrient quality and antioxidant system of cabbage (Brassica oleracea var. capitata L.).

The application of Se yeast as a Se source to cultivate Se-rich cabbage has a significant effect on cabbage growth and quality indices. Results showed that total plant weight, head weight, and head size in cabbage were notably increased by 48.4%, 88.3%, and 25.4% under 16 mg/kg Se yeast treatment, respectively. Compare with the control, a high proportion of 3874% of Se accumulation in cabbage head was also detected in 16 mg/kg Se yeast treatment. Selenocystine (SeCys2) and Methyl-selenocysteine (MeSeCys) were the main Se speciations in the cabbage head. Application of 8 mg/kg Se yeast improved cabbage quality and antioxidant system indices, including free amino acid, soluble sugar, ascorbic acid, phenolic acid, glucosinolates, and SOD activity, which had 81.6%, 46.5%, 34.9%, 12.3%, 44.8%, 25.2% higher than that of the control, respectively. In summary, considering 8 mg/kg Se yeast as the appropriate level of Se enrichment during cabbage cultivation. These findings enhanced our understanding of the effects of Se yeast on the growth and quality of cabbage and provided new insights into Se-enrichment vegetable cultivation.

Destructive Extraction and Enhanced Diffusion of Phospholipids on Lipid Membranes by Phosphorene Oxide Nanosheets.

Phosphorene is a novel two-dimensional nanomaterial with a puckered surface morphology, which has broad potential application prospects in the fields of biology and medicine. Phosphorene nanosheets are easily oxidized and form phosphorene oxide (PO) in an aerobic environment, whose biological effect remains unknown. In this paper, using large-scale molecular dynamics simulations, we show that the PO nanosheets can penetrate into and destructively extract large amounts of phospholipids from the lipid membrane. The PO nanosheets with a higher oxidation concentration have less extraction of phospholipids, while its oxidation mode has no effect on the extraction of phospholipids. Moreover, inserting PO nanosheets into the lipid membrane can enhance the diffusion of phospholipids on the membrane. These findings can shed light on understanding/designing the membrane-nanomaterial interactions.

Transcriptome, proteome, and metabolome reveal the mechanism of tolerance to selenate toxicity in Cardamine violifolia.

Cardamine violifolia was found here to accumulate selenium (Se) to over 9000 mg kg-1 dry weight. To investigate the mechanism of Se accumulation and tolerance in C. violifolia, metabolome, transcriptome, and proteome technologies were applied to C. violifolia seedlings treated with selenate. Several sulfate transporter (Sultr) genes (Sultr1;1, Sultr1;2, and Sultr2;1) and sulfur assimilatory enzyme genes showed high expression levels in response to selenate. Many calcium protein and cysteine-rich kinase genes of C. violifolia were downregulated, whereas selenium-binding protein 1 (SBP1) and protein sulfur deficiency-induced 2 (SDI2) of C. violifolia were upregulated by selenate. The expression of genes involved in the ribosome and posttranslational modifications and chaperones in C. violifolia were also detected in response to selenate. Based on the results of this study and previous findings, we suggest that the downregulated expression of calcium proteins and cysteine-rich kinases, and the upregulated expression of SBP1 and SDI2, were important contributors to the Se tolerance of C. violifolia. The downregulation of cysteine-rich kinases and calcium proteins would enhance Se tolerance of C. violifolia is a novel proposition that has not been reported on other Se hyperaccumulators. This study provides us novel insights to understand Se accumulation and tolerance in plants.

Sandwich method with or without lauromacrogol in the treatment of gastric variceal bleeding with liver cirrhosis: A meta-analysis.

BACKGROUND: To compare the efficacy and safety of the modified sandwich method with lauromacrogol in the treatment of gastric variceal bleeding (GVB) caused by liver cirrhosis with the traditional sandwich method no accompanied by lauromacrogol via a meta-analysis. METHODS: The Cochrane Library, Pubmed, the China National Knowledge Infrastructure (CNKI) database, the Chinese Wanfang database, and the Chongqing VIP database were searched to identify cohort studies comparing modified to traditional sandwich method in the treatment of GVB with liver cirrhosis. The relative risk for hemostasis rate, gastric varices (GV) remission rate, re-bleeding rate, the incidence of post-operative complications (pain, fever, ulcer or erosion, ectopic embolism), and all-cause mortality were calculated. The mean difference for average tissue adhesive dosage per case was calculated. Relevant data were analyzed with the Reviewer Manager 5.3.5. RESULTS: Four cohort studies with a total of 587 patients were included in this meta-analysis. In the treatment of GVB with liver cirrhosis, compared with the traditional sandwich method, the modified sandwich method was associated with a higher GV remission rate (RR: 1.24, 95% CI: 1.09-1.42; P = .001) according to the pooled results. There were no statistically significant differences between the 2 methods in the rate of hemostasis, re-bleeding, pain, fever, ulcer or erosion, ectopic embolism, and all-cause mortality (P ≧ .05). CONCLUSIONS: This meta-analysis indicated that the modified sandwich method with lauromacrogol is more effective than the traditional sandwich method without lauromacrogol. Due to the limited number of studies and samples, more RCT studies are needed to further validate the efficacy and safety of the modified sandwich method with lauromacrogol in the treatment of GVB with liver cirrhosis.