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Thyroid cancer is a great part of the endocrine tumor with an increasing incidence. Papillary thyroid carcinoma (PTC) is the most common subtype. With the enormous pace taken in the microarray technology, bioinformatics is applied in data mining more frequently. Weighted gene coexpression network analysis (WGCNA) can perform analysis combining clinic information. We performed WGCNA for prognostic genes associated with PTC. From the GEO profile, we got ten modules. We identified a key module that was closest to patients’ survival time. Then, we screened five hub genes (ATRX, BOD1L1, CEP290, DCAF16, and NEK1) from the key module based on the clinical information from TCGA. These five genes not only significantly differ between the normal and tumor groups but have prognostic value. The receiver operating characteristic (ROC) curve indicated that they had the potential to serve as prognostic genes. We performed next-generation sequencing using the PTC tissue to get more convincing evidence. Besides, we established a new signature and verified it through K-M plots and ROC. The signature could be an independent factor for the prognosis of PTC, and we built a nomogram to carry out a quantitative study. In a word, the hub genes we explored in the study deserved more basic and clinical research.

Yeshen Zhang,1,2,&ast; Zhengrong Xu,3,&ast; Wenfei He,4,&ast; Zehuo Lin,1,2 Yaoxin Liu,1,2 Yining Dai,1,2 Wei Chen,5 Weikun Chen,1,2 Wenlong He,1,2 Chongyang Duan,6 Pengcheng He,1,2 Yuanhui Liu,1,2 Ning Tan1,2 1Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People’s Republic of China; 3Department of Cardiology, People’s Hospital of Baoan Shenzhen, Guangzhou, People’s Republic of China; 4Department of Cardiology, Guangdong Provincial People’s Hospital’s Nanhai Hospital, the Second People’s Hospital of Nanhai District Foshan City, Foshan, People’s Republic of China; 5Department of Cardiology, Fujian Provincial Clinical College of Fujian Medical University, Fujian Provincial Hospital, Fujian Institute of Cardiovascular Disease, Fuzhou, People’s Republic of China; 6Department of Biostatistics, School of Public Health, Southern Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ning Tan; Yuanhui Liu, Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of China, Tel +86-20-83819161, Fax +86-20-83824369, Email gdtanning@126.com; liuyuanhui@gdph.org.cnBackground: The serum uric acid/albumin ratio (sUAR), a novel inflammatory marker, effectively predicts acute kidney injury (AKI) and cardiovascular outcomes. However, whether the sUAR predicts post-contrast acute kidney injury (PC-AKI) in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI) remains uncertain. In this study, we evaluated the association between the sUAR and PC-AKI in patients with STEMI undergoing PCI.Methods: We consecutively recruited patients with STEMI who underwent PCI and stratified them into three groups according to the terciles of the sUAR. The primary outcome was the incidence of PC-AKI. The association between the sUAR and PC-AKI was assessed by multivariate logistic regression analysis.Results: A total of 2861 patients with STEMI were included in this study. The incidence of PC-AKI increased stepwise with increasing sUAR tercile (2.6% vs 4.0% vs 11.6%, p < 0.001), and the incidence of in-hospital major adverse clinical events (MACEs) was highest among patients in the Q3 group. Multivariate logistic regression analysis revealed that the sUAR was also an independent predictor of PC-AKI (continuous sUAR, per 1-unit increase, odds ratio [OR] [95% confidence interval (CI)]: 1.06 [1.02– 1.10], p = 0.005; tercile of sUAR, OR [95% CI] for Q2 and Q3: 1.18 [0.69– 2.01] and 1.85 [1.12– 3.06], respectively, with Q1 as a reference) but not in-hospital MACEs. In the receiver operating characteristic (ROC) analysis, the area under the curve (AUC) of the sUAR for predicting PC-AKI was 0.708 (95% CI: 0.666– 0.751), and ROC analysis also showed that the sUAR was superior to uric acid and albumin alone in predicting PC-AKI.Conclusion: Increasing sUAR was significantly associated with a higher risk of PC-AKI but not in-hospital MACEs in patients with STEMI who underwent PCI, suggesting that sUAR had a predictive value for PC-AKI after PCI in patients with STEMI. Further studies are required to confirm this finding.Keywords: serum uric acid/albumin ratio, post-contrast acute kidney injury, ST-segment elevation myocardial infarction

This study investigated the effect of FoxM1 on the biological behavior of neuroblastoma (NB) cells in vitro and the association between FoxM1 and PI3K/AKT pathways in NB cell lines. Materials and m...

Antioxidants with high efficacy and low toxicity have the potential to treat cerebral ischemia reperfusion injury (CIRI). Dienone monocarbonyl curcumin analogs (DMCA) capable of overcoming the instability and pharmacokinetic defects of curcumin possess notable antioxidant activity but are found to be significantly toxic. In this study, a novel skeleton of the monoenone monocarbonyl curcumin analogue sAc possessing reduced toxicity and improved stability was designed on the basis of the DMCA skeleton. Moreover, 32 sAc analogs were obtained by applying a green, simple, and economical synthetic method. Multiple sAc analogs with an antioxidant protective effect in PC12 cells were screened using an H2O2-induced oxidative stress damage model, and quantitative evaluation of structure–activity relationship (QSAR) model with regression coefficient of R2 = 0.918921 was built through random forest algorithm (RF). Among these compounds, the optimally active compound sAc15 elicited a potent protective effect on cell growth of PC12 cells by effectively eliminating ROS generation in response to oxidative stress injury by activating the Nrf2/HO-1 antioxidant signaling pathway. In addition, sAc15 exhibited good protection against CIRI in the mice middle cerebral artery occlusion (MCAO) model. In this paper, we provide a novel class of antioxidants and a potential compound for stroke treatment.

Lu Diao,1,2 Jin Tao,2 Yiqi Wang,3 Ying Hu,1,2 Wenfei He1 1School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, People’s Republic of China; 2College of Pharmacy, Zhejiang Pharmaceutical College, Ningbo, Zhejiang 315100, People’s Republic of China; 3College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 311402, People’s Republic of ChinaCorrespondence: Ying HuCollege of Pharmacy, Zhejiang Pharmaceutical College, No. 888, East Section, Yinxian Main Road, The Zone of Higher Education, Ningbo, Zhejiang 315100, People’s Republic of ChinaTel +86 5748822 2707Fax +86 5748822 3023Email pharmhawk@126.comWenfei HeSchool of Pharmaceutical Sciences, Wenzhou Medical University, Ouhai District, Chashan Street, University Campus, Wenzhou, Zhejiang 325035 People’s Republic of ChinaTel +86 0577 86699572Email wenfeihe@126.comBackground and purpose: Systemic lupus erythematous (SLE) is an autoimmune disease caused by many factors. Lupus nephritis (LN) is a common complication of SLE and represents a major cause of morbidity and mortality. Previous studies have shown the advantages of multi-targeted therapy for LN and that TLR4 signaling is a target of anti-LN drugs. High-mobility group box 1 (HMGB1), a nuclear protein with a proinflammatory cytokine activity, binds specifically to TLR4 to induce inflammation. We aimed to develop PEGylated TAT peptide-cationic liposomes (TAT-CLs) to deliver anti-HMGB1 siRNA and dihydroartemisinin (DHA) to increase LN therapeutic efficiency and explore their treatment mechanism.Methods: We constructed the TAT-CLs-DHA/siRNA delivery system using the thin film hydration method. The uptake and localization of Cy3-labeled siRNA were detected by confocal microscopy and flow cytometry. MTT assays were used to detect glomerular mesangial cell proliferation. Real-time PCR, Western blot analysis, and ELISA evaluated the anti-inflammatory mechanism of TAT-CLs-DHA/siRNA.Results: We constructed the TAT-CLs-DHA/siRNA delivery system measuring approximately 140 nm with superior storage and serum stabilities. In vitro, it showed significantly greater uptake compared with unmodified liposomes and significant inhibition of glomerular mesangial cell proliferation. TAT-CLs-DHA/siRNA inhibited NF-κB activation in a concentration-dependent manner. Real-time PCR and Western blot analysis showed that TAT-CLs-DHA/siRNA downregulated expression of HMGB1 mRNA and protein. TAT-CLs-DHA/siRNA markedly diminished Toll-like receptor 4 (TLR4) expression and subsequent activation of MyD88, IRAK4, and NF-κB.Conclusion: TAT-CLs-DHA/siRNA may have the potential for treatment of inflammatory diseases such as LN mediated by the TLR4 signaling pathway.Keywords: cationic liposome, HMGB1 siRNA, DHA, Toll-like receptor 4

The supplementation of exogenous antioxidants to scavenge excessive reactive oxygen species (ROS) is an effective treatment for cerebral ischemia-reperfusion injury (CIRI) in stroke. Piperlongumine (PL), a natural alkaloid, has a great potential as a neuroprotective agent, but it also has obvious toxicity. Moreover, its neuroprotective effects remain to be improved. In this study, we designed a series of novel PL analogs by hybridizing the screened low-toxicity diketene skeleton with antioxidant effect and the 3,4,5-trimethoxyphenyl group, which may increase the antioxidant activity of PL. The intermediate was synthesized by a novel green synthesis method, and 34 compounds were obtained. The compounds without obvious cytotoxicity have remarkable antioxidant effects, especially compared with diketene skeletons and PL. The cytoprotection of the active compound decreased significantly by reduction of the carbon-carbon double bonds of the Michael acceptor in the diketene skeleton. More importantly, further study revealed that compound A9, which has the best activity, can confer protection for cells against oxidative stress and attenuate brain injury in vivo. Overall, this study provided a promising drug candidate for the treatment of CIRI and guided the further development of drug research in oxidative stress-mediated diseases.

Five new diterpenes, including an unprecedented 5,5,6,6,5-pentacyclic diterpene, sponalactone (1), two new spongian diterpenes, 17- O-acetylepispongiatriol (2) and 17- O-acetylspongiatriol (3), and two new spongian diterpene artifacts, 15α,16α-dimethoxy-15,16-dihydroepispongiatriol (4) and 15α-ethoxyepispongiatriol-16(15 H)-one (5), were isolated from a South China Sea collection of the marine sponge Spongia officinalis, together with three known analogues (6-8). The structures of the new diterpenes were elucidated by extensive spectroscopic analysis. The absolute configurations were established on the basis of ECD data. Compounds 1-5 and 7 exhibited moderate inhibition against LPS-induced NO production in RAW264.7 macrophages with IC

Four new steroids, named 7-dehydroerectasteroid F (1), 11α-acetoxyarmatinol A (2), 22,23-didehydroarmatinol A (3), and 3-O-acetylhyrtiosterol (4), together with 11 previously described analogues, were isolated from a South China Sea collection of the soft coral Dendronephthya gigantea. The structures of the new steroids were elucidated by comprehensive spectroscopic analysis and by comparison with previously reported data. Compound 1 showed potent protection against H2O2-induced oxidative damage in neuron-like PC12 cells by promoting nuclear translocation of Nrf2 and enhancing the expression of HO-1. 1 represents the first steroid-type antioxidant from marine organisms.

Scavenging reactive oxygen species (ROS) by antioxidants is the important therapy to cerebral ischemia-reperfusion injury (CIRI) in stroke. The antioxidant with novel dual-antioxidant mechanism of directly scavenging ROS and indirectly through antioxidant pathway activation may be a promising CIRI therapeutic strategy. In our study, a series of chalcone analogues were designed and synthesized, and multiple potential chalcone analogues with dual antioxidant mechanisms were screened. Among these compounds, the most active 33 not only conferred cytoprotection of H2O2-induced oxidative damage in PC12 cells through scavenging free radicals directly and activating NRF2/ARE antioxidant pathway at the same time, but also played an important role against ischemia/reperfusion-related brain injury in animals. More importantly, in comparison with mono-antioxidant mechanism compounds, 33 exhibited higher cytoprotective and neuroprotective potential in vitro and in vivo. Overall, our findings showed compound 33 could emerge as a promising anti-ischemic stroke drug candidate and provided novel dual-antioxidant mechanism strategies and concepts for oxidative stress-related diseases treatment., Graphical abstract Chalcone analogue 33 conferred protection of PC12 cells against H2O2 insult with novel dual-antioxidant mechanism of directly scavenging reactive oxygen species (ROS) and indirectly through antioxidant pathway activation, and the effect of 33 was more pronounced than that of mono-antioxidant mechanism compounds after MCAO and BCAO in animals.fx1

Curcumin, a natural product, has been shown to exhibit notable anti-inflammatory activities. However, the clinical application of curcumin was restricted by its poor stability and bioavailability. We have reported a series of monocarbonyl analogs of curcumin (MACs) previously. In the present study, we synthesized 32 semi-conservative MACs and evaluated their anti-inflammatory effects in RAW 264.7 macrophages. Most of them showed enhanced abilities to inhibit the lipopolysaccharide (LPS)-induced expression of tumor necrosis factor alpha (TNF-α). The preliminary structure–activity relationship was discussed and the preliminary anti-inflammatory mechanism was also explored. The most potent analog compound, WZ35, exhibits significant protection against LPS-induced death in septic mice. These findings suggest that this kind of curcumin derivative may be used to develop promising anti-inflammatory agents to treat inflammatory diseases.

Yali Zhang,1,2,* Chengguang Zhao,1,2,* Wenfei He,2,* Zhe Wang,2 Qilu Fang,2 Bing Xiao,2 Zhiguo Liu,2 Guang Liang,2 Shulin Yang1 1School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing, Jiangsu, People's Republic of China; 2Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, University Town, Wenzhou, Zhejiang, People's Republic of China *These authors contributed equally to this work Abstract: Sepsis is a systemic inflammatory response syndrome and is mainly caused by lipopolysaccharides (LPS) – a component of the cell walls of gram-negative bacteria, via toll-like receptor 4–mitogen-activated protein kinases/nuclear factor-kappa B-dependent proinflammatory signaling pathway. Here, we synthesized 26 asymmetric monocarbonyl analogs of curcumin and evaluated their anti-inflammatory activity by inhibiting the LPS-induced secretion of tumor necrosis factor-α and interleukin-6 in mouse RAW264.7 macrophages. Five active compounds (3a, 3c, 3d, 3j, and 3l) exhibited dose-dependent inhibition against the release of tumor necrosis factor-α and interleukin-6, and they also showed much higher chemical stability than curcumin in vitro. The anti-inflammatory activity of analogs 3a and 3c may be associated with their inhibition of the phosphorylation of extracellular signal-regulated kinase and the activation of nuclear factor-kappa B. In addition, 3c exhibited significant protection against LPS-induced septic death in vivo. These results indicate that asymmetrical monocarbonyl curcumin analogs may be utilized as candidates for the treatment of acute inflammatory diseases. Keywords: sepsis, inflammatory cytokines, anti-inflammation, quantitative structure–activity relationship

Propofol is currently one of the most widely used intravenous anesthetic. In the present study, we investigated the effects of propofol on neuropathogenesis in newborn rats under hypoxic conditions. Seven-day old SD rats were assigned into one of the six treatments: propofol+50% oxygen (propofol-oxygen, PO), propofol+room air (propofol-air, PA), propofol+18% oxygen (propofol-hypoxia, PH), control group: lipid emulsion solvent+50% oxygen (CO), lipid emulsion solvent+room air (CA), lipid emulsion solvent+18% oxygen (CH). The rats assigned to anesthesia or control groups received intraperitoneally (ip) propofol 50 mg/kg or identical volume of lipid emulsion solvent (5.0 ml/kg) for seven days. SaO(2) (%) and respiratory rate (RR) were monitored throughout the procedures. The rats were decapitated 24h after 7 days exposure. TUNEL staining, Nissl staining, ultrastructural changes and the expression of caspase-3 in the brain tissues were assessed. We found propofol-induced attenuation of respiration could produce lower oxygen concentrations in the blood (hypoxia) under air or mild hypoxia conditions. Interestingly, in the presence of oxygen completely rescued hypoxia to normal levels, suggesting that propofol-induced respiratory depression led to hypoxia only under air or mild hypoxic conditions (propofol/hypoxia). In addition, propofol indirectly induced apoptosis through hypoxia resulting from respiratory depression under air or hypoxic conditions, which was determined by elevated expression of caspase-3, increased TUNEL-positive cells, ultrastructural changes of neuronal cell death and loss of Nissl staining neuronal in infant SD rat brains. However, in propofol-oxygen group and all control groups, no significant apoptosis were observed. These findings indicated that propofol per se or hypoxia per se did not directly induce significant apoptosis. However, propofol-induced attenuation of respiration could produce lower oxygen concentrations in the blood under air or mild hypoxia conditions and thereby result in neuronal degeneration. So, it is important to supply with supplementary oxygen during propofol anesthesia.

Gentiana straminea Maxim. has been used widely as a traditional Chinese medicine for the treatment of rheumarthritis, icterepatitis, constipation, pain and hypertension. Five secoiridoids, gentiopicroside (GTP), 6′-O-(2-hydroxy-3-O-β-d–glucopyranosyl-benzoyl)-sweroside (HGBS), 6′-O-β-d-glucosylgentiopicroside (GGTP), sweroside (SW) and swertiamarin (STM) were isolated from the roots of G. straminea. The effect of these secoiridoids on stimulus-induced superoxide generation in human neutrophils was assayed by measuring the reduction of ferricytochrome c. Tyrosyl or serine/threonine phosphorylation of neutrophil proteins, and translocation of the cytosolic compounds to the cell membrane were also investigated using specific monoclonal antibodies. The five secoiridoids used in the present experiment suppressed N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced superoxide generation in a concentration dependent manner. GTP and HGBS also suppressed phorbol 12-myristate 13-acetate (PMA) and arachidonic acid (AA)-induced superoxide generation. However, the other three secoiridoids showed no effect on PMA- and AA-induced superoxide generation. fMLP-, PMA- and AA-induced tyrosyl or serine/threonine phosphorylation and translocation of the cytosolic proteins to the cell membrane were suppressed in parallel with the suppression of the stimulus-induced superoxide generation. Copyright © 2011 John Wiley & Sons, Ltd.

In the current study, we developed a nanosphere bio-barcode technology to detect trace gonyautoxin 2/3 (GTX 2/3). GTX 2/3-glucose oxidase (GOX) conjugates were first prepared as the coating antigen in a periodate reaction. Subsequently, gold nanoparticles (NP) dual-labeled with anti-GTX 2/3 monoclonal antibodies (Mab) and DNA oligonucleotides were synthesized via a one-step preparation method. Combining PCR with indirect competitive ELISA (icELISA), a novel immunosorbent bio-barcode assay was established utilizing the Mab-NP-dsDNA complex to convert enzymatic signals to DNA signals. Importantly, the limit of detection of the method was lower than 0.74 microg mL(-1). Thus, the immunosorbent bio-barcode assay is a rapid and high-throughput screening tool to detect GTX 2/3 in aquatic products.

We investigated the effects of various sulfur amino acids on the phosphorylation of proteins and the translocation of cytosolic compounds to cell membrane in stimulus-treated human neutrophils using specific monoclonal antibodies. D,L-homocysteine and D,L-homocysteine-thiolactone enhanced fMLP-induced tyrosyl phosphorylation of proteins and the translocation of p47phox, p67phox, and rac to the cell membrane in a concentration-dependent manner. L-cystathionine, NAc-L-cysteine and carboxymethylcysteine suppressed the tyrosyl phophorylation and translocation of cytosolic compounds to the cell membrane. L-cystathionine, L-cysteine and NAc-L-cysteine suppressed PMA-induced serine/threonine phosphorylation and the translocation of cytosolic compounds to the cell membrane. L-cysteine, NAc-L-cysteine and D,L-homocysteine enhanced AA-induced serine/threonine phosphorylation and the translocation of cytosolic compounds to the cell membrane, but L-cystathionine had opposite effects. These results indicated that the effects of sulfur amino acids on tyrosyl or serine/threonine phosphorylation and the translocation of p47phox, p67phox, and rac to the cell membrane in the stimulus-treated human neutrophils were in parallel with those of the stimulus-induced superoxide generation reported in previous paper. L-cysteine, D,L-homocysteine and L-cystathionine weakly inhibited lipid peroxidation, but the other sulfur amino acids tested had no effect.

Sepsis, an acute inflammatory disease, remains the most common cause of death in intensive care units. A series of benzimidazole and imidazopyridine derivatives were synthesized and screened for anti-inflammatory activities, and the imidazopyridine series showed excellent inhibition of the expression of inflammatory cytokines in LPS-stimulated macrophages. Compounds X10, X12, X13, X14, and X15 inhibited TNF-α and IL-6 release in a dose-dependent manner, and X12 showed no cytotoxicity in hepatic cells. Furthermore, X12 exhibited a significant protection against LPS-induced septic death in mouse models. Together, these data present a series of new imidazopyridines with potential therapeutic effects in acute inflammatory diseases.

Five oleanolic acid triterpenoid saponins (OTS-1, 2, 3, 4 and 5) were isolated from the rhizome of Anemone raddeana. The effect of these triterpenoid saponins on stimulus-induced superoxide generation in human neutrophils was assayed by measuring the reduction of ferricytochrome c using a dual-beam spectrophotometer. The phosphorylation of neutrophil proteins, and translocation of p67(phox), p47(phox) and Rac to plasma membrane were investigated using specific monoclonal antibodies. The five oleanolic acid triterpenoid saponins used in this experiment suppressed N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced superoxide generation in a concentration-dependent manner. OTS-1, 2 and 4 suppressed phorbol 12-myristate 13-acetate (PMA)- and arachidonic acid (AA)-induced superoxide generation in a concentration-dependent manner, but OTS-3 and 5 showed no effect. fMLP- and PMA-induced tyrosyl or serine/threonine phosphorylation, and fMLP-, PMA- and AA-induced translocation of p67(phox), p47(phox) and Rac to plasma membrane were in parallel with the suppression of the stimulus-induced superoxide generation.

Gentiana straminea Maxim. has been used widely as a traditional Chinese medicine for the treatment of rheumarthritis, icterepatitis, constipation, pain and hypertension. Five secoiridoids, gentiopicroside (GTP), 6'-O-(2-hydroxy-3-O-β-D-glucopyranosyl-benzoyl)-sweroside (HGBS), 6'-O-β-D-glucosylgentiopicroside (GGTP), sweroside (SW) and swertiamarin (STM) were isolated from the roots of G. straminea. The effect of these secoiridoids on stimulus-induced superoxide generation in human neutrophils was assayed by measuring the reduction of ferricytochrome c. Tyrosyl or serine/threonine phosphorylation of neutrophil proteins, and translocation of the cytosolic compounds to the cell membrane were also investigated using specific monoclonal antibodies. The five secoiridoids used in the present experiment suppressed N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced superoxide generation in a concentration dependent manner. GTP and HGBS also suppressed phorbol 12-myristate 13-acetate (PMA) and arachidonic acid (AA)-induced superoxide generation. However, the other three secoiridoids showed no effect on PMA- and AA-induced superoxide generation. fMLP-, PMA- and AA-induced tyrosyl or serine/threonine phosphorylation and translocation of the cytosolic proteins to the cell membrane were suppressed in parallel with the suppression of the stimulus-induced superoxide generation.

Four triterpenoid compounds hederacolchiside E (1), hederasaponin B (2), raddeanoside 20 (3) and raddeanoside 21 (4) were isolated from ethanol extracts of rhizome of Anemone raddeana Regel. The effects of these triterpenoids on superoxide generation, tyrosyl phosphorylation of proteins and translocation of cytosolic compounds, such as p47phox, p67phox and Rac to the cell membrane in human neutrophils was investigated. The superoxide generation induced by N-formyl-methionyl-leucyl-phenylalanine (fMLP) was slightly suppressed by hederasaponin B, raddeanoside 20 and raddeanoside 21 in a concentration dependent manner. The superoxide generation induced by arachidonic acid (AA) was suppressed by hederasaponin B and raddeanoside 21 significantly. fMLP- and AA-induced tyrosyl phosphorylation and translocation of the cytosolic proteins: p47phox, p67phox, and Rac to the cell membrane were suppressed in parallel with the suppression of stimulus-induced superoxide generation.

The effects of five ginsenosides (G-Rh2, -Rd, -Rb1, -Rb2, -Rh1) isolated from the root of Panax gingseng on stimulus-induced superoxide generation in human neutrophils were evaluated by measuring the reduction of ferricytochrome c. The tyrosyl or serine/threonine phosphorylation of neutrophil proteins and translocation of p47phox, p67phox, and Rac to the plasma membrane were detected using specific monoclonal antibodies. G-Rh2 significantly suppressed superoxide generation induced by N-formylmethionyl-leucylphenylalanine (fMLP), phorbol 12-myristate 13-acetate (PMA), and arachidonic acid (AA) in a concentration-dependent manner. G-Rh1 showed a comparably lower suppression on fMLP-induced superoxide generation. G-Rd, -Rb1, and -Rb2 also suppressed AA-induced superoxide generation in high concentrations. G-Rd and G-Rb1 showed no effect on fMLP- and PMA-induced superoxide generation. FMLP-, PMA-, and AA-induced tyrosyl or serine/threonine phosphorylation and translocation of p47phox, p67phox, and Rac to the plasma membrane were in parallel with the suppression of the stimulus-induced superoxide generation.

Chengguang Zhao,1,2,* Yali Zhang,1,2,* Peng Zou,1 Jian Wang,3 Wenfei He,2 Dengjian Shi,2 Huameng Li,2 Guang Liang,2 Shulin Yang1 1School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing, 2Chemical Biology Research Center, School of Pharmaceutical Sciences, 3Department of Orthopedics, The 1st Affiliated Hospital, Wenzhou Medical University, Wenzhou, People’s Republic of China *These authors contributed equally to this work Abstract: A novel class of asymmetric mono-carbonyl analogs of curcumin (AMACs) were synthesized and screened for anti-inflammatory activity. These analogs are chemically stable as characterized by UV absorption spectra. In vitro, compounds 3f, 3m, 4b, and 4d markedly inhibited lipopolysaccharide (LPS)-induced expression of pro-inflammatory cytokines tumor necrosis factor-α and interleukin-6 in a dose-dependent manner, with IC50 values in low micromolar range. In vivo, compound 3f demonstrated potent preventive and therapeutic effects on LPS-induced sepsis in mouse model. Compound 3f downregulated the phosphorylation of extracellular signal-regulated kinase (ERK)1/2 MAPK and suppressed IκBα degradation, which suggests that the possible anti-inflammatory mechanism of compound 3f may be through downregulating nuclear factor kappa binding (NF-κB) and ERK pathways. Also, we solved the crystal structure of compound 3e to confirm the asymmetrical structure. The quantitative structure–activity relationship analysis reveals that the electron-withdrawing substituents on aromatic ring of lead structures could improve activity. These active AMACs represent a new class of anti-inflammatory agents with improved stability, bioavailability, and potency compared to curcumin. Our results suggest that 3f may be further developed as a potential agent for prevention and treatment of sepsis or other inflammation-related diseases. Keywords: asymmetric mono-carbonyl analogs of curcumin (AMACs), stability, anti-inflammatory property, sepsis, QSAR&nbsp

Correction for 'Synthesis and biological evaluation of novel semi-conservative monocarbonyl analogs of curcumin as anti-inflammatory agents' by Zhe Wang et al., Med. Chem. Commun., 2015, DOI: 10.1039/c5md00114e.