Preparation, characterization, antioxidant, and antifungal activity of phenyl/indolyl-acyl chitooligosaccharides.

In this study, carboxylic acids compounds were grafted onto chitooligosaccharides to prepare seven phenyl/indolyl-acyl chitooligosaccharides derivatives. The structures of the derivatives were characterized by IR spectroscopy, 13C NMR and elemental analysis. Meanwhile, antioxidant activities in vitro of the novel derivatives were analyzed. Compared to COS and carboxylic acid, the derivatives showed higher scavenging capacity for superoxide anion and DPPH radicals, with scavenging rates of 59.39% and 94.86%, respectively. The hydroxyl radical scavenging ability of the derivatives was only 18.89%. The antifungal activities of chitooligosaccharide derivatives against Diaporthe batatas and Phytophthora capsici were studied by the growth rate method. Compared with chitooligosaccharide itself, derivatives were inhibited by 97.77% and 100%. The above results showed that chitooligosaccharide derivatives have good biocompatibility and can be used in food, agriculture and medicine.

[Gene expression profiling of testicular seminoma via bioinformatical analysis].

OBJECTIVE: To investigate the differentially expressed genes related to the survival of testicular seminoma patients and the pathogenesis of the malignancy. METHODS: We obtained the gene expression profiling of testicular seminoma data set GSE8607 from the GEO database and differentially expressed genes in testicular seminoma using the GEO2R online tool. We performed GO and KEGG pathway enrichment via the DAVID website, screened testicular seminoma-related core genes using the STRING and Cytoscape software, and analyzed the survival rate and expression level associated with the core genes through the Kaplan Meier plotter and GEPIA websites. RESULTS: Totally, 591 differentially expressed genes were identified, of which 216 were up-regulated and mainly enriched in 23 biological processes, 8 cell components, 5 biological functions and 7 KEGG pathways, and the other 375 down-regulated and enriched only in the biological process, involving the formation and development of spermatozoa. Thirty-two core genes were obtained via PPI network analysis, including C1QB, CCL2, CCR2, GPR183, ELL, LAPTM5, NPY5R, CD28 and MMP9, which were closely related to the survival rate (P < 0.05), C1QB, CCL2, CCR2, SELL, LAPTM5, CD28 and MMP9, which were highly expressed in the testicular seminoma tissue (P < 0.05), and NPY5R, which was lowly expressed in the testicular seminoma tissue (P < 0.05). CONCLUSIONS: The 8 differentially expressed genes identified in the testicular seminoma tissue contribute to effective prediction of the survival rate of the patients as well as to the diagnosis, prevention and treatment of the disease and development of new anti-cancer drugs.

Association of elevated inflammatory markers and severe COVID-19: A meta-analysis.

Our study aimed to assess the existing evidence on whether severe coronavirus disease 2019 (COVID-19) is associated with elevated inflammatory markers.The PubMed, Embase, Web of Science, Scopus, Chinese National Knowledge Infrastructure, WanFang, and China Science and Technology Journal databases were searched to identify studies published between January 1 and April 21, 2020 that assayed inflammatory markers in COVID-19 patients. Three reviewers independently examined the literature, extracted relevant data, and assessed the risk of publication bias before including the meta-analysis studies.Fifty-six studies involving 8719 COVID-19 patients were identified. Meta-analysis showed that patients with severe disease showed elevated levels of white blood cell count (WMD: 1.15, 95% CI: 0.78-1.52), C-reactive protein (WMD: 38.85, 95% CI: 31.19-46.52), procalcitonin (WMD: 0.08, 95% CI: 0.06-0.11), erythrocyte sedimentation rate (WMD: 10.15, 95% CI: 5.03-15.46), interleukin-6 (WMD: 23.87, 95% CI: 15.95-31.78), and interleukin-10 (WMD: 2.12, 95% CI: 1.97-2.28). Similarly, COVID-19 patients who died during follow-up showed significantly higher levels of white blood cell count (WMD: 4.11, 95% CI: 3.25-4.97), C-reactive protein (WMD: 74.18, 95% CI: 56.63-91.73), procalcitonin (WMD: 0.26, 95% CI: 0.11-0.42), erythrocyte sedimentation rate (WMD: 10.94, 95% CI: 4.79-17.09), and interleukin-6 (WMD: 59.88, 95% CI: 19.46-100.30) than survivors.Severe COVID-19 is associated with higher levels of inflammatory markers than a mild disease, so tracking these markers may allow early identification or even prediction of disease progression.

Risk factors of severe cases with COVID-19: a meta-analysis.

Our study aimed to systematically analyse the risk factors of coronavirus disease 2019 (COVID-19) patients with severe disease. An electronic search in eight databases to identify studies describing severe or critically ill COVID-19 patients from 1 January 2020 to 3 April 2020. In the end, we meta-analysed 40 studies involving 5872 COVID-19 patients. The average age was higher in severe COVID-19 patients (weighted mean difference; WMD = 10.69, 95%CI 7.83-13.54). Patients with severe disease showed significantly lower platelet count (WMD = -18.63, 95%CI -30.86 to -6.40) and lymphocyte count (WMD = -0.35, 95%CI -0.41 to -0.30) but higher C-reactive protein (CRP; WMD = 42.7, 95%CI 31.12-54.28), lactate dehydrogenase (LDH; WMD = 137.4, 95%CI 105.5-169.3), white blood cell count（WBC), procalcitonin（PCT）, D-dimer, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and creatinine（Cr）. Similarly, patients who died showed significantly higher WBC, D-dimer, ALT, AST and Cr but similar platelet count and LDH as patients who survived. These results indicate that older age, low platelet count, lymphopenia, elevated levels of LDH, ALT, AST, PCT, Cr and D-dimer are associated with severity of COVID-19 and thus could be used as early identification or even prediction of disease progression.

CT imaging features of 4121 patients with COVID-19: A meta-analysis.

OBJECTIVE: We systematically reviewed the computed tomography (CT) imaging features of coronavirus disease 2019 (COVID-19) to provide reference for clinical practice. METHODS: Our article comprehensively searched PubMed, FMRS, EMbase, CNKI, WanFang databases, and VIP databases to collect literatures about the CT imaging features of COVID-19 from 1 January to 16 March 2020. Three reviewers independently screened literature, extracted data, and assessed the risk of bias of included studies, and then, this meta-analysis was performed by using Stata12.0 software. RESULTS: A total of 34 retrospective studies involving a total of 4121 patients with COVID-19 were included. The results of the meta-analysis showed that most patients presented bilateral lung involvement (73.8%, 95% confidence interval [CI]: 65.9%-81.1%) or multilobar involvement (67.3%, 95% CI: 54.8%-78.7%) and just little patients showed normal CT findings (8.4%). We found that the most common changes in lesion density were ground-glass opacities (68.1%, 95% CI: 56.9%-78.2%). Other changes in density included air bronchogram sign (44.7%), crazy-paving pattern (35.6%), and consolidation (32.0%). Patchy (40.3%), spider web sign (39.5%), cord-like (36.8%), and nodular (20.5%) were common lesion shapes in patients with COVID-19. Pleural thickening (27.1%) was found in some patients. Lymphadenopathy (5.4%) and pleural effusion (5.3%) were rare. CONCLUSION: The lung lesions of patients with COVID-19 were mostly bilateral lungs or multilobar involved. The most common chest CT findings were patchy and ground-glass opacities. Some patients had air bronchogram, spider web sign, and cord-like. Lymphadenopathy and pleural effusion were rare.

Global transcriptional regulation of STAT3- and MYC-mediated sepsis-induced ARDS.

BACKGROUND: In recent years, sepsis-induced acute respiratory distress syndrome (ARDS) has remained a major clinical challenge for patients in intensive care units. While some progress has been reported over the years, the pathogenesis of ARDS still needs to be further expounded. METHODS: In the present study, gene set enrichment analysis, differentially expressed genes analysis, short time-series expression miner, protein-protein interaction (PPI) networks, module analysis, hypergeometric test, and functional enrichment analysis were performed in whole blood gene expression profiles of sepsis and induced-sepsis ARDS to explore the molecular mechanism of sepsis-induced ARDS. RESULTS: Further dysregulated genes in the process evolving from healthy control through sepsis to sepsis-induced ARDS were identified and organized into 10 functional modules based on their PPI networks. These functional modules were significantly involved in cell cycle, ubiquitin mediated proteolysis, spliceosome, and other pathways. MYC, STAT3, LEF1, and BRCA1 were potential transcription factors (TFs) regulating these modules. A TF-module-pathway global regulation network was constructed. In particular, our findings suggest that MYC and STAT3 may be the key regulatory genes in the underlying dysfunction of sepsis-induced ARDS. Receiver operating characteristic curve analysis showed the core genes in the global regulation network may be biomarkers for sepsis or sepsis-induced ARDS. CONCLUSIONS: We found that MYC and STAT3 may be the key regulatory genes in the underlying dysfunction of sepsis-induced ARDS. The reviews of this paper are available via the supplementary material section.

Identification of novel bioactive metabolites of 5-demethylnobiletin in mice.

SCOPE: Biotransformation of dietary components is important for their in vivo biological activities after oral ingestion. Herein, we investigated biotransformation of 5-demethylnobiletin (a polymethoxyflavone found in citrus fruits) in mice, and its implication in the inhibition of human colon cancer cells. METHODS AND RESULTS: Urine samples were collected from mice fed with 5-demethylnobiletin (1) and analyzed by LC-ESI-MS and HPLC coupled with an electrochemical detector. Three major metabolites were identified as 5,3'-didemethylnobiletin (2), 5,4'-didemethylnobiletin (3), and 5,3',4'-tridemethylnobiletin (4) by comparing their ESI-MS and HPLC profiles with those of authentic standards synthesized by a multistep route. Cell viability assay in human colon cancer cells demonstrated that all three metabolites of 5-demethylnobiletin, especially 5,3'-didemethylnobiletin (2), showed much stronger inhibitory effects on cancer cell growth than 5-demethylnobiletin. For example, metabolites (2-4) showed IC50 of 0.12, 5.5, and 4.2 µM in SW620 cells, respectively, while 5-demethylnobiletin at 10 µM only caused 37% inhibition after 72 h of treatment. CONCLUSION: Three novel metabolites were identified in mice after oral administration of 5-demethylniobiletin. These metabolites exhibited strong inhibitory effects against human colon cancer cells. Our results provide a first report on these bioactive metabolites and warrant further investigation on their molecular mechanism of actions.

[Identification of the IgE-binding epitopes in main dust mite allergen Der p 1].

OBJECTIVE: To identify the IgE-binding epitopes in the allergen Der p 1 of main house dust mites, which can be recognized by the specific IgE in the sera from allergic individuals, and obtain a hypoallergen derived from the T-B epitope fused peptide for potential use in specific immunotherapy (SIT). METHODS: Thirty-one peptides containing 15 amino acids each, which covered the full 222 amino acids of Der p 1 protein sequence, were synthesized on the cellulous membrane by solid-phase peptide (SPOTs) synthesis, with 8 overlapping amino acids between every two neighboring peptides. The membrane bearing the spots of the synthesized peptides were incubated with the allergic serum pools consisting of the sera from 5 allergic individuals. The membrane was then probed with HRP-conjugated anti-human IgE, followed by enhanced chemiluminescence (ECL) for visualization and gray scale analysis of the positive peptide spots. RESULTS: Three strong IgE-binding epitopes were identified in the amino acid sequence of Der p 1 molecule, namely Ep1 (amino acids 85-99), Ep2 (amino acids 106-120) and Ep3 (amino acids 190-204). CONCLUSION: The 3 IgE-binding epitopes (B cell epitopes) identified in Der p 1 confirm the presence of linear epitopes in Der p 1, suggesting the possibility of constructing T/B epitope-fused hypoallergens.

The antioxidant activity of 2-(4(or 2)-hydroxyl-5-chloride-1,3-benzene-di-sulfanimide)-chitosan.

Chitosan (CS) with two different molecular weights was modified by reacting with 4-hydroxyl-5-chloride-1,3-benzene-disulfo-chloride or 2-hydroxyl-5-chloride-1,3-benzene-disulfo-chloride to give new 2-(4(or 2)-hydroxyl-5-chloride-1,3-benzene-di-sulfanimide)-chitosan (2-HCBSAHCS, 2-HCBSALCS, 4-HCBSAHCS, 4-HCBSALCS). The structure of the derivatives was characterized by FT-IR and 13C NMR spectroscopy. The antioxidant activities of the derivatives were investigated employing various established systems, such as hydroxyl radical (.OH)/superoxide anion (O2.-) scavenging/reducing power and chelating activity. All the derivatives showed stronger scavenging activity on hydroxyl radical than chitosan and ascorbic acid (Vc), and IC50 of 4-HCBSAHCS, 4-HCBSALCS, 2-HCBSAHCS and 2-HCBSALCS was 0.334, 0.302, 0.442, 0.346 mg/mL, respectively. The inhibitory activities of the derivatives toward superoxide radical by the PMS-NADH system were strong. The results showed that the superoxide radical scavenging effect of 2-(4(or 2)-hydroxyl-5-chloride-1,3-benzene-di-sulfanimide)-chitosan was higher than chitosan. The derivatives had obviously reducing power and slight chelating activity. The data obtained in in vitro models clearly establish the antioxidant potency of 2-(4(or 2)-hydroxyl-5-chloride-1,3-benzene-disulfanimide)-chitosan.