Tumor PKCδ instigates immune exclusion in EGFR-mutated non-small cell lung cancer.

BACKGROUND: The recruitment of a sufficient number of immune cells to induce an inflamed tumor microenvironment (TME) is a prerequisite for effective response to cancer immunotherapy. The immunological phenotypes in the TME of EGFR-mutated lung cancer were characterized as non-inflamed, for which immunotherapy is largely ineffective. METHODS: Global proteomic and phosphoproteomic data from lung cancer tissues were analyzed aiming to map proteins related to non-inflamed TME. The ex vivo and in vivo studies were carried out to evaluate the anti-tumor effect. Proteomics was applied to identify the potential target and signaling pathways. CRISPR-Cas9 was used to knock out target genes. The changes of immune cells were monitored by flow cytometry. The correlation between PKCδ and PD-L1 was verified by clinical samples. RESULTS: We proposed that PKCδ, a gatekeeper of immune homeostasis with kinase activity, is responsible for the un-inflamed phenotype in EGFR-mutated lung tumors. It promotes tumor progression by stimulating extracellular matrix (ECM) and PD-L1 expression which leads to immune exclusion and assists cancer cell escape from T cell surveillance. Ablation of PKCδ enhances the intratumoral penetration of T cells and suppresses the growth of tumors. Furthermore, blocking PKCδ significantly sensitizes the tumor to immune checkpoint blockade (ICB) therapy (αPD-1) in vitro and in vivo model. CONCLUSIONS: These findings revealed that PKCδ is a critical switch to induce inflamed tumors and consequently enhances the efficacy of ICB therapy in EGFR-mutated lung cancer. This opens a new avenue for applying immunotherapy against recalcitrant tumors.

Chelidonine selectively inhibits the growth of gefitinib-resistant non-small cell lung cancer cells through the EGFR-AMPK pathway.

Tyrosine kinase inhibitors (TKIs) have been widely used for the clinical treatment of patients with non-small cell lung cancer (NSCLC) harboring mutations in the EGFR. Unfortunately, due to the secondary mutation in EGFR, eventual drug-resistance is inevitable. Therefore, to overcome the resistance, new agent is urgently required. Chelidonine, extracted from the roots of Chelidonium majus, was proved to effectively suppress the growth of NSCLC cells with EGFR double mutation. Proteomics analysis indicated that mitochondrial respiratory chain was significantly inhibited by chelidonine, and inhibitor of AMPK effectively blocked the apoptosis induced by chelidonine. Molecular dynamics simulations indicated that chelidonine could directly bind to EGFR and showed a much higher binding affinity to EGFRL858R/T790M than EGFRWT, which demonstrated that chelidonine could selectively inhibit the phosphorylation of EGFR in cells with EGFR double-mutation. In vivo study revealed that chelidonine has a similar inhibitory effect like second generation TKI Afatinib. In conclusion, targeting EGFR and inhibition of mitochondrial function is a promising anti-cancer therapeutic strategy for inhibiting NSCLC with EGFR mutation and TKI resistance.

[Chemical constituents from fresh tubers of Dioscorea bulbifera].

Eighteen compounds were isolated from the 95% ethanol extract of fresh tubers of Dioscorea bulbifera by column chromatography over silica gel,Sephadex LH-20, and ODS. Their structures were elucidated by spectroscopic data analysis as 6-hydroxy-2,10,10-trimethoxy-anthracen-9-one(1), diosgenin (2), stigmasterol(3), 3, 7-dimethoxy-5, 3', 4'-trihydroxyflavone(4), 2, 7-dihydroxy-3, 4-dimethoxyphenanthrene(5), 3, 7-dihydroxy-2, 4-dimethoxy phenanthrene(6), 2, 7-dihydroxy-4-methoxyphenanthrene (7), 2, 7-dihydroxy-3, 4-dimethoxy-9, 10-dihydroxy phenanthrene(8), azelaic acid (9), 8-epidiosbulbin E acetate (10), 1, 7-bis-(4-hydroxyphenyl)-4E, 6E-heptadien-3-one(11), diosbulbin B(12), pentacosanoic acid 2', 3'-dihydroxypropyl ester(13), 2, 7-dihydroxy-4-methoxy-9, 10-dihydroxy-phenanthrene (14), 1, 7-bis-(4-hydroxyphenyl)-1E, 4E, 6E-heptatrien-3-one (15), 6-ethoxy-1H-pyrimidine-2, 4-dione (16), 3, 5, 4'-trihydroxy-bibenzyl (17), and diosbulbin F (18). Compound 1 is a new compound, and compounds 7, 9, 13, and 16 were isolated from this plant for the first time.

Two New Alkaloids from the Roots of Baphicacanthus cusia.

Phytochemical investigation of the root of Baphicacanthus cusia (NEES) BREMEK afforded two new alkaloids, baphicacanthin A (1) and baphicacanthin B (2), along with 28 known compounds. The chemical structures of these compounds were elucidated on the basis of one and two dimensional (1D/2D)-NMR and high resolution (HR)-MS spectral evidence.

Effect of acupuncture on CXCL8 receptors in rats suffering from embryo implantation failure.

To observe the effect of acupuncture on CXCL8 receptors (CXCR1 and CXCR2) in rat endometrium experiencing embryo implantation failure, 72 pregnant rats were randomly divided into four groups: normal group (N), embryo implantation failure group (M), acupuncture treatment group (A), and progestin treatment group (W). Then the rats in each group were equally randomized into a day-6 (D6) group, a day-8 (D8) group, and a day-10 (D10) group. The rats in group M, group A, and group W were treated with mifepristone-sesame oil solution on day 1, while the rats in group N were injected with the same amount of sesame oil. Meanwhile, "Housanli" and "Sanyinjiao" were selected for acupuncture. From day 1 to the time of death, the rats in group A were fastened up and then acupuncture was administered while the rats in group N and group M were only fixed, and the rats in group W were given progestin. The number of implanted embryos was calculated. The expression of CXCR1 and CXCR2 in rat endometrium was detected by immunohistochemistry, Western blotting and real-time PCR. Compared to group N, the average number of implanted embryos, the protein and mRNA expression of CXCR1 (D6, D8 and D10), and the protein and mRNA expression of CXCR2 (D8 and D10) in rat endometrium were significantly decreased in group M. Compared to group M, there was significant elevation in the average number of implanted embryos, the protein expression (D6, D8 and D10) and mRNA expression (D8) of CXCR1 in rat endometrium of group A, and the protein expression (D8 and D10) and mRNA expression (D8) of CXCR2 in rat endometrium of group W. These findings indicated that acupuncture can increase the number of implanted embryos in rats of embryo implantation failure, which may be relevant with up-regulation the expression of CXCR1 and CXCR2 at maternal-fetal interface of rats with embryo implantation failure.

Clinical Efficacy and Safety of Bevacizumab, Apatinib, and Recombinant Human Endothelial Inhibitor in the Treatment of Advanced Gastric Cancer.

OBJECTIVE: To investigate the clinical efficacy and safety of bevacizumab, apatinib, and recombinant human endothelial inhibitor in the treatment of advanced gastric cancer. METHODS: The medical data of 204 patients with a medium to advanced gastric cancer assessed for eligibility treated in our hospital from February 2019 to April 2020 were retrospectively analyzed. The eligible patients were assigned at a ratio of 1 : 1:1 : 1 to either the control group (chemotherapy), study group I (bevacizumab combined with chemotherapy), study group II (apatinib combined with chemotherapy), or study group III (recombinant human endothelial inhibitor combined with chemotherapy) according to different treatment methods. The treatment efficacy, drug toxicity, quality of life, and serum tumor marker levels before and after treatment were compared among the four groups. RESULTS: Regarding the treatment effects, the effective rate of study group II (68.63%) was significantly higher than that of the control group (33.33%), study group I (58.82%), and study group III (49.02%) (P < 0.05). The four groups showed similar safety and tolerability profiles (P > 0.05). The treatment in study group II led to a significantly higher physiological function score vs. the other three groups, but the scores of other items were not significantly different. Significant reduction was observed in the serum tumor markers after treatment in the four groups (P < 0.05), but treatment in study group II led to a significantly greater reduction than the other three groups (P < 0.05). CONCLUSION: The addition of apatinib, bevacizumab, and recombinant human endothelial inhibitor injection to chemotherapy for the treatment of medium to advanced gastric cancer can significantly improve the clinical treatment efficacy, among which the use of apatinib combined with chemotherapy achieves the best results, which is worthy of clinical promotion.

[Effects of nutritional preparation on HPO axis function and energy metabolism in uterus and ovary of rats exposed to intermittent cold].

Objective: To investigate the effects of a self-designed nutritional preparation on hypothalamic-pituitary-ovarian (HPO) axis function and energy metabolism in female SD rats exposed to intermittent cold. Methods: Female SD rats were divided into control group, cold exposure group and nutritional preparation group. The control group and cold exposure group were given distilled water by daily gavage, and the nutritional preparation group was given nutritional preparation intragastrically. After the treatment, the cold exposure group and nutritional preparation group were exposed to -10℃ in a cabin for 4 h every day. After being treated for 14 days, the serum, uterus and ovary of rats were collected. The serum follicle stimulating hormone (FSH), luteinizing hormone (LH) and other hormone indicators were detected by enzyme-linked immunosorbent assay (ELISA) and colorimetry was used to detect ATPase and other energy metabolism related indicators. Results: Compared with the control group, cold exposure significantly up-regulated the protein expressions of FSHR and LHR, and notably enhanced the activity of Na+-K+-ATPase and Ca2+-Mg2+-ATPase in ovary and uterus (P<0.05). Nutritional preparation down-regulated the protein expressions of FSHR and LHR, and inhibited the activity of ATPase in ovary and uterus (P<0.05) compared with the cold exposure group. Conclusion: Nutritional preparations can effectively improve the expressions of HPO axis related receptors and abnormal energy metabolism in uterus and ovary caused by intermittent cold exposure.

[Antifatigue effects of the composition of Moringa oleifera leaves and Polygonatum polysaccharide and its mechanisms].

Objective: To investigate the anti-fatigue effects of composition of Moringa oleifera leaves and Polygonatum polysaccharide, and to explore the mechanisms. Methods: Thirty male Kunming mice were randomly divided into control (C) and composition of Moringa oleifera leaves and Polygonatum polysaccharide group (MP). There were 15 mice in each group. Group C was given distilled water and the group MP was given composition intragastriclly every day. The volume was 0.5 ml. After 14 days of treatment, weight-bearing swimming experiment was conducted, and exhaustive swimming time was recorded. The bearing weight was 3% of the body weight. In another experiment, 48 male Kunming mice were randomly divided into quiet control group (QC), swimming control group (SC) and composition group (MP). There were 16 mice in each group. The QC and SC groups were given distilled water intragastrically, and the group MP was treated with composition every day for 14 days. The volume was 0.5 ml. On the day 15, 30 minutes after intragastriclly administration of distilled water, blood, liver and hind leg muscle of the QC group were collected immediately. The SC and MP groups were subjected non-weight-bearing swimming experiment, and blood, liver and hind leg muscle were collected after swimming. The fatigue related indexes, oxidant/antioxidant parameters and energy metabolism indicators in serum and tissues were determined by commercial kits. Results: The exhaustive swimming time of mice in MP group was significantly longer than that in the C group (P<0.05). Compared with the control group, non-weight-bearing swimming decreased the contents of serum glucose and GSH, the contents of hepatic glycogen and ATP, the hepatic activities of SOD, LDH and ATPase, and muscle activity of GSH-Px (P< 0.05). However, serum levels of BUN and MDA were increased (P<0.05). Compared with the SC group, the composition remarkably increased the contents of serum glucose and hepatic glycogen, increased serum content of GSH, enhanced hepatic activities of SOD, LDH and ATPase and muscle activity of GSH-Px, and increased the hepatic content of ATP (P<0.05). However, the serum level of BUN was decreased (P<0.05). Conclusion: The Moringa oleifera leaves and Polygonatum polysaccharide composition possesses anti-fatigue effects. Anti-oxidant and improving energy metabolism could be the important mechanisms.

Inhibition of MIR4435-2HG on Invasion, Migration, and EMT of Gastric Carcinoma Cells by Mediating MiR-138-5p/Sox4 Axis.

BACKGROUND: The previous investigations have identified that long non-coding RNA (lncRNAs) act as crucial regulators in gastric carcinoma. However, the function of lncRNA MIR4435-2HG in the modulation of gastric carcinoma remains elusive. Here, we aimed to explore the role of MIR4435-2HG in gastric carcinoma. METHOD: The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were applied to select the differently expressed lncRNAs in gastric carcinoma. The qRT-PCR was applied to analyze MIR4435-2HG expression in carcinoma tissues and cell lines. The effect of MIR4435-2HG on proliferation, invasion, migration, and apoptosis of gastric carcinoma cells was detected by Cell Counting Kit-8 (CCK-8) assays, transwell assays, and flow cytometry in vitro. A subcutaneous tumor model was constructed to examine the tumor growth of gastric carcinoma cells after knocking out MIR4435-2HG. RNA immunoprecipitation and luciferase reporting assays were applied to evaluate the interaction of MIR4435-2HG, miR-138-5p, and Sox4. RESULTS: The bioinformatics analysis based on TCGA and GEO databases indicated that MIR4435-2HG was obviously elevated in gastric carcinoma samples. The qRT-PCR analysis revealed that MIR4435-2HG was upregulated in clinical gastric carcinoma tissues and cells. The high expression of MIR4435-2HG is associated with the poor survival rate of patients. The knockout of MIR4435-2HG could repress the proliferation, invasion, migration, and epithelial-mesenchymal transition (EMT) and accelerate the apoptosis of gastric carcinoma cells. Moreover, the deletion of MIR4435-2HG was able to attenuate the tumor growth in vivo. Mechanically, we identified that MIR4435-2HG enhanced Sox4 expression by directly interacting with miR-138-5p as a competitive endogenous RNA (ceRNA) in gastric carcinoma cells, in which Sox4 was targeted by miR-138-5p. CONCLUSION: MIR4435-2HG is elevated in gastric carcinoma cells and contributes to the growth, metastasis, and EMT of gastric carcinoma cells by targeting miR-138-5p/Sox4 axis. MIR4435-2HG may be applied as a potential therapeutic target in gastric carcinoma.

Metabolomic study on vitamins B1, B2, and PP supplementation to improve serum metabolic profiles in mice under acute hypoxia based on ¹H NMR analysis.

OBJECTIVE: To explore metabolic changes after acute hypoxia and modulating effect of vitamins B1, B2, and PP supplementation in mice exposed to acute hypoxia. METHODS: Fifty male Kunming mice were randomly divided into 5 groups: normal, acute hypoxia, acute hypoxia with 2, 4 and 8 time-vitamins B1, B2, and PP supplementation. All mice were fed with corresponding diets for two weeks and then were exposed to a simulated altitude of 6,000 meters for 8 h, except for the normal group. Nuclear magnetic resonance analysis was used to identify the changes of serum metabolic profiles. RESULTS: There were significant changes in some serum metabolites under induced acute hypoxia, essentially relative increase in the concentrations of lactate, sugar and lipids and decrease in ethanol. The serum levels of choline, succinate, taurine, alanine, and glutamine also increased and phosphocholine decreased in the acute hypoxia group. After vitamins B1, B2, and PP supplementation, all these metabolic changes gradually recovered. CONCLUSIONS: Significant changes in serum metabolic profile were observed by metabolomics in mice exposed to acute hypoxia, and vitamins B1, B2, and PP supplementation proved to be beneficial to improving some metabolic pathways. It is suggested that the dietary intakes of vitamins B1, B2, and PP should be increased under hypoxia condition.

Quality evaluation of Hypericum japonicum by using high-performance liquid chromatography coupled with photodiode array detector and electrospray ionization tandem mass spectrometry.

A high-performance liquid chromatography coupled with photodiode array detection and electrospray ionization tandem mass spectrometry (HPLC-PAD-ESI-MS(n)) method was developed to evaluate the quality of Hypericum japonicum through establishing chromatographic fingerprint and simultaneous determination of seven phenolic compounds. The analysis was achieved on an Ultimate XB-C(18) analytical column (250 mm x 4.6 mm i.d., 5 microm) using an aqueous solution of acetic acid (pH 3.8) and methanol as the mobile phase. Ten samples of H. japonicum from various habitats were investigated and the correlation coefficients of similarity were determined from the HPLC fingerprints. By using an online ESI-MS(n), 20 common peaks in chromatographic fingerprints were identified as phenols, including flavones and their glycosides, flavonones and their glucosides, flavanols, xanthones, phloroglucinols, phenyl propanoids and chromones. Based on the above study, seven phenols which are considered to be major constituents in H. japonicum, including 3,4-dihydroxybenzoic acid (1), taxfolin-7-O-alpha-L-rhamnoside (7), 7-dihydroxy-2-(1-methylpropyl)chromone-8-beta-D-glucoside (8), isoquercitrin (14), quercitrin (16), quercetin-7-O-alpha-L-rhamnoside (18) and quercetin (19) were quantified by the validated HPLC-PAD method. This developed method by combination of chromatographic fingerprint and quantification analysis could be applied to control the quality of H. japonicum.

Agaritine and its derivatives are potential inhibitors against HIV proteases.

Agaritine, or beta-N-[gamma-L(+)-glutamyl]-4-hydroxymethylphenylhydrazine, is a Chinese herbal medicine, known having the antiviral and anticancer function. However, so far no reports whatsoever have been made for its potential as an anti-HIV agent. It was observed by docking experiments for more than 9,000 compounds extracted from various Chinese medicines that the compound agaritine distinguished itself from all the others in binding to the HIV protease with the most favorable free energy. Based on this, a series of derivatives were generated by modifying agaritine. It has been observed thru an extensive docking study that some of agaritine derivatives had markedly stronger binding interaction with the HIV protease than agaritine, suggesting that these derivatives might be good candidates for developing drugs for AIDS therapy.

Computational approach to drug design for oxazolidinones as antibacterial agents.

A three dimensional Quantitative Structure Activity Relationship (3D-QSAR) model for a series of (S)-3-Aryl-5-substituted oxazolidinones was developed to gain insights into the design for potential new antibacterial agents. It was found that the Comparative Molecular Field Analysis (CoMFA) method yielded good results while the Comparative Molecular Similarity Indices Analysis (CoMSIA) was less satisfactory. The CoMFA method yielded a cross-validated correlation coefficient q(2) = 0.681, non-cross-validated R(2) = 0.991, SE (Standard Error ) = 0.054, and the value of statistical significance measure F = 266.98. The relative steric and electrostatic contributions are 0.542 and 0.458, respectively. These results indicate that the model possesses a high predictivity. Guided by this model, three new compounds were synthesized. All these compounds exhibit inhibitory activity; two of them were shown having high activity (MIC = 1.0 microg/ml). The activity observed by experiments was in good agreement with the theoretical one. It is anticipated that the present model would be of value in facilitating design of new potent antibacterial agents.

[Effects of MAPKs inhibitors on GSH metabolic enzymes in rat hepatocytes].

OBJECTIVE: To investigate the effects of mitogen-activated protein kinases (MAPKs) inhibitors on glutathione (GSH) metabolism, and to explore the pathway related to GSH metabolism. METHODS: BRL rat hepatocytes were treated by c-Jun NH2-terminal kinase (JNK),p38, and extracellular signal-regulated kinase 1/2 (ERK1/2) inhibitors:SP600125, SB203580 and PD98659, respectively, for 24 h. MTT method was used to measure hepatocytes viability. The content of GSH was determined by high performance liquid chromatography. The protein expressions of JNK and phosphorylated JNK (p-JNK) was tested by Luminex method. Activities of GSH metabolic enzymes were detected by commercial kits. RESULTS: Hepatocytes vitality was inhibited when the concentrations of SP600125, SB203580 and PD98659 were higher than 10 µmol/L, 20 µmol/L, and 40 µmol/L, respectively; SP600125 decreased the content of GSH in hepatocytes, while SB203580 and PD98659 had no effect. SP600125 reduced p-JNK protein expression, and enhanced GSH-Px activity significantly. CONCLUSIONS: JNK MAPK pathway takes part in the GSH metabolism in hepatocytes.

A method to identify trace sulfated IgG N-glycans as biomarkers for rheumatoid arthritis.

N-linked glycans on immunoglobulin G (IgG) have been associated with pathogenesis of diseases and the therapeutic functions of antibody-based drugs; however, low-abundance species are difficult to detect. Here we show a glycomic approach to detect these species on human IgGs using a specialized microfluidic chip. We discover 20 sulfated and 4 acetylated N-glycans on IgGs. Using multiple reaction monitoring method, we precisely quantify these previously undetected low-abundance, trace and even ultra-trace N-glycans. From 277 patients with rheumatoid arthritis (RA) and 141 healthy individuals, we also identify N-glycan biomarkers for the classification of both rheumatoid factor (RF)-positive and negative RA patients, as well as anti-citrullinated protein antibodies (ACPA)-positive and negative RA patients. This approach may identify N-glycosylation-associated biomarkers for other autoimmune and infectious diseases and lead to the exploration of promising glycoforms for antibody therapeutics.Post-translational modifications can affect antibody function in health and disease, but identification of all variants is difficult using existing technologies. Here the authors develop a microfluidic method to identify and quantify low-abundance IgG N-glycans and show some of these IgGs can be used as biomarkers for rheumatoid arthritis.

[Screening of new HIV inhibitors based on the database of traditional Chinese medicine].

AIM: To report the preliminary result of the HIV inhibitor screening based on cheminformatics tools and the traditional Chinese medicine database. METHODS: Database search was carried out with saquinavir molecule as a template, further screening was made with docking. Detailed studies using molecular dynamics simulation of 50 ps and 200 ps were made with respect to a potential leading compound, leucovorin. RESULTS: The leucovorin molecule distinguished from other molecules as a potential drug candidate and is subject to extensive studies. The bonding profile and energy were calculated with MD simulations. CONCLUSION: Our results could be very helpful when we modify leucovorin or design new inhibitors against HIV.

[Function of getting rid of cores of Cornus officinalis Sieb. et Zucc. and studies on method of processing in producing area].

OBJECTIVE: To gain a clear idea on function of getting fid of cores of Cornus officinalis Sieb. et Zucc. and elect a suitable processing method and technics of Crnus officinalis Sieb. et Zucc. in producing area. METHODS: The contents of loganin and morroniside were determined in the cores and sarocarp of Cornus officinalis Sieb. et Zucc.; Using pathogonal method, the methods which Cornus officinalis sieb. et Zuee. were warmed or poached were isolated by determining quantitively loganin from Cornus officinalis Sieb. et Zucc. by HPLC. RESULTS: There was a bit loganin and morroniside in the cores of Cornus officinalis Sieb. et Zuecc.; There were three aspects that were marked influence to extracted account of loganin which were hot temperature of poach, adding water and time of warming. The best suitable extracting technology was warmed in 60 degrees C by 10 min and then getted rid of cores. CONCLUSION: Clearing the non-medicinal positon is the function of getting rid of cores of Cornus officinalis Sieb. et Zucc. and warming is better than poach.

Microfluidic Chip-LC/MS-based Glycomic Analysis Revealed Distinct N-glycan Profile of Rat Serum.

The rat is an important alternative for studying human pathology owing to certain similarities to humans. Glycomic studies on rat serum have revealed that variations in the N-glycans of glycoproteins correlated with disease progression, which is consistent with the findings in human serum. Therefore, we comprehensively characterized the rat serum N-glycome using microfluidic chip-LC-ESI-QTOF MS and MS/MS techniques. In total, 282 N-glycans, including isomers, were identified. This study is the first to present comprehensive profiling of N-glycans containing O-acetylated sialic acid, among which 27 N-glycans are novel. In addition, the co-existence of N-acetylneuraminic acid (NeuAc) and N-glycolylneuraminic acid (NeuGc) in a single N-glycan ('mixed' N-glycan) was detected and represents a new type of N-glycan in rat serum. The existence of O-acetylated sialic acid is the characteristic feature of rat serum that distinguishes it from mouse and human sera. Comparisons between the rat, mouse, and human serum glycomes revealed that the rat glycome is more similar to that of human sera than to that of mouse sera. Our findings highlight the similarities between the glycomic profile of rat and human sera and provided important selection criteria for choosing an appropriate animal model for pathological and pharmacological studies.

Glycomic signatures on serum IgGs for prediction of postvaccination response.

Millions of individuals are vaccinated worldwide each year to stimulate their adaptive immune systems to produce protective antibodies and T-cell response against pathogens. Since glycosylation of the Fc region of immunoglobulin G (IgG) can be influenced by the host's immune status, it was inferred that glycosylation profile of IgG might be altered as a result of the immune response. Therefore, subclass-specific glycosylation profiles of serum IgGs from 26 healthy adults before and after vaccination with a trivalent subunit influenza virus vaccine were comprehensively analyzed to explore glycomic signatures for vaccination. The results showed that no significant changes in the glycosylation of total IgGs took place before and after vaccination, but distinct glycosylation profiles in responders (fourfold or more increase of HI titer after vaccination) and nonresponders (less than fourfold increase of HI titer) were observed. This difference between the responders and nonresponders occurred even in the resting state. On the basis of variable importance parameters, glycosylation markers that distinguish responders from nonresponders were identified. These markers can be used as molecular signatures to predict antibody titers after vaccination. This is the first study of serum IgG glycosylation profiles in healthy adults receiving a trivalent inactivated influenza vaccine.

Quantitative comparison and metabolite profiling of saponins in different parts of the root of Panax notoginseng.

Although both rhizome and root of Panax notoginseng are officially utilized as notoginseng in "Chinese Pharmacopoeia", individual parts of the root were differently used in practice. To provide chemical evidence for the differentiated usage, quantitative comparison and metabolite profiling of different portions derived from the whole root, as well as commercial samples, were carried out, showing an overall higher content of saponins in rhizome, followed by main root, branch root, and fibrous root. Ginsenoside Rb2 was proposed as a potential marker with a content of 0.5 mg/g as a threshold value for differentiating rhizome from other parts. Multivariate analysis of the metabolite profile further suggested 32 saponins as potential markers for the discrimination of different parts of notoginseng. Collectively, the study provided comprehensive chemical evidence for the distinct usage of different parts of notoginseng and, hence, is of great importance for the rational application and exploitation of individual parts of notoginseng.