Effect of Thin-Walled Radial Sheath for Large-Bore Access On Reducing Periprocedural Radial Artery Occlusion Following Complex PCI: The REDUCE-RAO Randomized Trial.

Background: Transradial artery (TRA) access for percutaneous coronary intervention (PCI) was associated with lower risks of major bleeding and vascular complications compared to transfemoral artery access. Use of large-bore ( ≥ 7-Fr) guiding catheters through TRA approach increased the likelihood of radial artery occlusion (RAO). This study aimed to investigate whether use of the thin-walled 7-Fr Glidesheath Slender, allowing PCI with large-caliber guiding catheters, is superior to standard 7-Fr Cordis sheath with respect to periprocedural RAO within 24 hours after transradial coronary intervention (TRI) in complex lesions. Methods: A prospective randomized, controlled, single-blinded (patient-blinded) trial was conducted, randomizing 504 patients with TRI for complex lesions to either 7-Fr Glidesheath Slender or conventional 7-Fr Cordis sheath. The primary outcome was defined as the incidence of periprocedural RAO with Doppler ultrasound during the first 24 hours after TRI. Results: The incidence of early RAO was 10.3% for 7-Fr Glidesheath Slender and 13.5% for conventional 7-Fr sheath (p = 0.271). The procedural success rate for Glidesheath Slender was 92.9% and for Cordis sheath was 93.7% (p = 0.722). There was no signficiant difference between treatment arms in terms of local hematoma and radial spasm, whereas use of the Glidesheath Slender was associated with significantly less pain during the procedure (numeric rating scale [NRS], 2.27 ± 0.75 vs. 2.45 ± 0.95, p = 0.017). The assessment of radial artery in ultrasound parameters after complex TRI was improved with Glidesheath Slender. Conclusions: Among patients with complex coronary lesions undergoing TRI, 7-Fr Glidesheath Slender was not superior to conventional 7-Fr in the prevention of periprocedural RAO within 24 hours following complex PCI, without reducing RAO occurrence. Clinical Trial Registration: NCT04748068.

Development of modified siRNA molecules incorporating 5-fluoro-2'-deoxyuridine residues to enhance cytotoxicity.

Therapeutic small interfering RNAs (siRNAs) are composed of chemically modified nucleotides, which enhance RNA stability and increase affinity in Watson-Crick base pairing. However, the precise fate of such modified nucleotides once the siRNA is degraded within the cell is unknown. Previously, we demonstrated that deoxythymidine release from degraded siRNAs reversed the cytotoxicity of thymidylate synthase (TS)-targeted siRNAs and other TS inhibitor compounds. We hypothesized that siRNAs could be designed with specific nucleoside analogues that, once released, would enhance siRNA cytotoxicity. TS-targeted siRNAs were designed that contained 5-fluoro-2'-deoxyuridine (FdU) moieties at various locations within the siRNA. After transfection, these siRNAs suppressed TS protein and messenger RNA expression with different efficiencies depending on the location of the FdU modification. FdU was rapidly released from the siRNA as evidenced by formation of the covalent inhibitory ternary complex formed between TS protein and the FdU metabolite, FdUMP. These modified siRNAs exhibited 10-100-fold greater cytotoxicity and induced multiple DNA damage repair and apoptotic pathways when compared with control siRNAs. The strategy of designing siRNA molecules that incorporate cytotoxic nucleosides represents a potentially novel drug development approach for the treatment of cancer and other human diseases.

Development and validation of a model integrating clinical and coronary lesion-based functional assessment for long-term risk prediction in PCI patients.

OBJECTIVES: To establish a scoring system combining the ACEF score and the quantitative blood flow ratio (QFR) to improve the long-term risk prediction of patients undergoing percutaneous coronary intervention (PCI). METHODS: In this population-based cohort study, a total of 46 features, including patient clinical and coronary lesion characteristics, were assessed for analysis through machine learning models. The ACEF-QFR scoring system was developed using 1263 consecutive cases of CAD patients after PCI in PANDA III trial database. The newly developed score was then validated on the other remaining 542 patients in the cohort. RESULTS: In both the Random Forest Model and the DeepSurv Model, age, renal function (creatinine), cardiac function (LVEF) and post-PCI coronary physiological index (QFR) were identified and confirmed to be significant predictive factors for 2-year adverse cardiac events. The ACEF-QFR score was constructed based on the developmental dataset and computed as age (years)/EF (%) + 1 (if creatinine ≥ 2.0 mg/dL) + 1 (if post-PCI QFR ≤ 0.92). The performance of the ACEF-QFR scoring system was preliminarily evaluated in the developmental dataset, and then further explored in the validation dataset. The ACEF-QFR score showed superior discrimination (C-statistic = 0.651; 95% CI: 0.611-0.691, P < 0.05 versus post-PCI physiological index and other commonly used risk scores) and excellent calibration (Hosmer-Lemeshow χ2 = 7.070; P = 0.529) for predicting 2-year patient-oriented composite endpoint (POCE). The good prognostic value of the ACEF-QFR score was further validated by multivariable Cox regression and Kaplan-Meier analysis (adjusted HR = 1.89; 95% CI: 1.18-3.04; log-rank P < 0.01) after stratified the patients into high-risk group and low-risk group. CONCLUSIONS: An improved scoring system combining clinical and coronary lesion-based functional variables (ACEF-QFR) was developed, and its ability for prognostic prediction in patients with PCI was further validated to be significantly better than the post-PCI physiological index and other commonly used risk scores.

Effects of acute slackline exercise on executive function in college students.

Background: Physical exercise as an intervention for improving cognitive function, especially executive function, is receiving increasing attention because it is easily accessible, cost-effective and promises many additional health-related benefits. While previous studies focused on aerobic exercise and resistance exercise, recent findings have suggested that exercise with high coordination demand elicits beneficial effects on executive function. We therefore examined the effects of an acute slackline exercise on the executive functions of young adults. Methods: In a crossover experimental design, 47 healthy participants (21 females), ranging in age from 18 to 27 years (M = 19.17, SD = 1.94) were randomly assigned to different sequences of two conditions (slackline exercise and film-watching). Before and after the 50 min intervention, a modified Simon task was used to assess participants' executive function (inhibitory control and cognitive flexibility). Results: College students showed better inhibitory control performance as indicated by shorter reaction times following acute slackline exercise than those who participated in the film-watching session. As there was no difference in accuracy between the slackline exercise and film-watching sessions, the shortened reaction time after slackline exercise provides evidence against a simple speed-accuracy trade-off. Conclusion: Compared with film-watching, acute slackline exercise provides favorable effects on executive function necessitating inhibition in young adults. These findings provide insight into exercise prescription and cognition, and further evidence for the beneficial effects of coordination exercise on executive functions.

Anti-inflammatory constituents from Phyllostachys makinoi Hayata.

A novel chromone analogue, phyllomakin A (1), and a new flavonolignan, (-)-quiquelignan C (2), along with 18 phenolic and 2 triterpenoids, were isolated from the leaves of Phyllostachys makinoi Hayata. The structures of 1-22 were elucidated by an application of various spectroscopic analyses (1D & 2D NMR and MS) and compared with reported data. A biological evaluation showed that compound 3 had very potent anti-NO production activity (IC50 = 4.80 µM), while compounds 2, 6, 11, and 15 showed moderate inhibitory effects (IC50 = 10.19, 13.26, 13.56, and 10.96 µM, respectively) without affecting cell viability at 20 µM.

Methyl-1-hydroxy-2-naphthoate, a novel naphthol derivative, inhibits lipopolysaccharide-induced inflammatory response in macrophages via suppression of NF-κB, JNK and p38 MAPK pathways.

OBJECTIVE AND DESIGN: The anti-inflammatory effect of methyl-1-hydroxy-2-naphthoate (MHNA), a novel naphthol derivative, was evaluated in the lipopolysaccharide (LPS)-induced inflammatory response in murine macrophages. MATERIALS AND METHODS: The release of nitric oxide (NO), interleukin-1beta (IL-1ß) and interleukin-6 (IL-6) were detected by the Griess reagent and ELISA methods. The protein expressions of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) were examined by Western blotting. The mRNA expressions of IL-1ß, IL-6, iNOS and COX-2 were determined by real-time PCR. Activation of mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-κB) pathways were detected by Western blotting, reporter gene assay and electrophoretic mobility shift assay. RESULTS: MHNA significantly inhibited the release of NO, IL-1ß and IL-6 as well as the protein expression of iNOS and COX-2 in LPS-stimulated macrophages. It also inhibited the mRNA expression of iNOS, COX-2, IL-1ß and IL-6. Further studies indicated that MHNA inhibited LPS-induced increases in NF-κB DNA-binding activity and NF-κB transcriptional activity as well as IκB-α degradation and NF-κB translocation in a dose-dependent manner. Meanwhile, the activation of p38 MAPK and c-Jun N-terminal kinases (JNK) induced by LPS were decreased by MHNA. CONCLUSIONS: MHNA inhibits the LPS-induced inflammatory response in murine macrophages via suppression of NF-κB and MAPKs signaling pathways activation.

Praeruptorin A inhibits lipopolysaccharide-induced inflammatory response in murine macrophages through inhibition of NF-κB pathway activation.

Praeruptorin A (PA) is a pyranocoumarin compound isolated from the dried root of Peucedanum praeruptorum Dunn (Umbelliferae). However, the antiinflammatory effect of PA has not been reported. The present study investigated the antiinflammatory effect of PA in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. PA significantly inhibited the LPS-induced production of nitric oxide (NO), interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α). The mRNA and protein expressions of inducible nitric oxide synthase (iNOS), IL-1ß and TNF-α were also suppressed by this compound. Further study showed that PA decreased the cytoplasmic loss of inhibitor κB-α (IκB-α) protein and inhibited the translocation of NF-κB from cytoplasm to nucleus. Taken together, the results suggest that PA may exert antiinflammatory effects in vitro in LPS-stimulated RAW 264.7 macrophages through inhibition of NF-κB signal pathway activation.

[A new natural polyphenol BJA32531 inhibited the proliferation and regulated miRNA expression in human HepG2 hepatocarcinoma cells].

OBJECTIVE: To study the effect of 1,2,6-Tri-O-galloyl-beta-D-glucopyranose (BJA32531) on the miRNA expression during BJA32531-induced cytotoxicity in human HepG2 hepatocarcinoma cells. METHODS: Cell proliferation was assessed using a colorimetric assay (cell counting kit-8). Apoptosis was assessed by annexin V and propidium iodide staining. The miRNA expression profile of the cancer cells was analyzed by a miRNA array and quantitative real-time PCR. RESULTS: BJA32531 inhibited the cell proliferation and increased apoptosis in HepG2 cancer cells. Cellular exposure to BJA32531 influenced the miRNA expression pattern in the cells, including 19 upregulated and 85 down-regulated miRNAs in the cells. The up-regulations of let-7a and miR-10b as well as the down-regulations of miR-132 and miR-125b were verified to be consistent with the the results of the miRNA array. CONCLUSION: Our study suggests that the mechanisms by which BJA32531 exerted the antiproliferative effects on HepG2 cancer cells may be related to its regulation of miRNA.

Geniposide inhibits high glucose-induced cell adhesion through the NF-kappaB signaling pathway in human umbilical vein endothelial cells.

AIM: To investigate whether geniposide, an iridoid glucoside extracted from gardenia jasminoides ellis fruits, inhibits cell adhesion to human umbilical vein endothelial cells (HUVECs) induced by high glucose and its underlying mechanisms. METHODS: HUVECs were isolated from human umbilical cords and cultured. The adhesion of monocytes to HUVECs was determined using fluorescence-labeled monocytes. The mRNA and protein levels of vascular cell adhesion molecule-1 (VCAM-1) and endothelial selectin (E-selectin) were measured using real-time RT-PCR and ELISA. Reactive oxygen species (ROS) production was measured using a fluorescent probe. The amounts of nuclear factor-kappa B (NF-kappaB) and inhibitory factor of NF-kappaB (IkappaB) were determined using Western blot analysis. The translocation of NF-kappaB from the cytoplasm to the nucleus was determined using immunofluorescence. RESULTS: Geniposide (10-20 mumol/L) inhibited high glucose (33 mmol/L)-induced adhesion of monocytes to HUVECs in a dose-dependent manner. This compound (5-40 mumol/L) also inhibited high glucose-induced expression of VCAM-1 and E-selectin at the gene and protein levels. Furthermore, geniposide (5-20 micromol/L) decreased ROS production and prevented IkappaB degradation in the cytoplasm and NF-kappaB translocation from the cytoplasm to the nucleus in HUVECs. CONCLUSION: Geniposide inhibits the adhesion of monocytes to HUVECs and the expression of CAMs induced by high glucose, suggesting that the compound may represent a new treatment for diabetic vascular injury. The mechanism underlying this inhibitory effect may be related to the inhibition of ROS overproduction and NF-kappaB signaling pathway activation by geniposide.

Effect of astragaloside IV on hepatic glucose-regulating enzymes in diabetic mice induced by a high-fat diet and streptozotocin.

AIM: Hepatic glycogen phosphorylase (GP) and glucose-6-phosphatase (G6Pase) are important in control of blood glucose homeostasis, and are considered to be potential targets for antidiabetic drugs. Astragaloside IV has been reported to have a hypoglycemic effect. However, the biochemical mechanisms by which astragaloside IV regulates hepatic glucose-metabolizing enzymes remain unknown. The present study examines whether GP and G6Pase mediate the hypoglycemic effect of astragaloside IV. METHODS: Type 2 diabetic mice were treated with astragaloside IV for 2 weeks. Blood glucose and insulin levels were measured by a glucometer and the ELISA method, respectively. Total cholesterol (TC) and triglyceride (TG) levels were determined using Labassay kits. Activities of hepatic GP and G6Pase were measured by the glucose-6-phosphate dehydrogenase-coupled reaction. The mRNA and protein levels of both enzymes were determined by real-time RT-PCR and Western blotting. RESULTS: Astragaloside IV at 25 and 50 mg/kg significally decreased the blood glucose, TG and insulin levels, and inhibited the mRNA and protein expression as well as enzyme activity of GP and G6Pase in diabetic mice. CONCLUSIONS: Astragaloside IV exhibited a hypoglycemic effect in diabetic mice. The hypoglycemic effect of this compound may be explained, in part, by its inhibition of hepatic GP and G6Pase activities.

Effect of geniposide, a hypoglycemic glucoside, on hepatic regulating enzymes in diabetic mice induced by a high-fat diet and streptozotocin.

AIM: Hepatic glycogen phosphorylase (GP) and glucose-6-phosphatase (G6Pase) play an important role in the control of blood glucose homeostasis and are proposed to be potential targets for anti-diabetic drugs. Geniposide is an iridoid glucoside extracted from Gardenia jasminoides Ellis fruits and has been reported to have a hypoglycemic effect. However, little is known about the biochemical mechanisms by which geniposide regulates hepatic glucose-metabolizing enzymes. The present study investigates whether the hypoglycemic effect of geniposide is mediated by GP or G6Pase. METHODS: Type 2 diabetic mice, induced by a high-fat diet and streptozotocin injection, were treated with or without geniposide for 2 weeks. Blood glucose levels were monitored by a glucometer. Insulin concentrations were analyzed by the ELISA method. Total cholesterol (TC) and triglyceride (TG) levels were measured using Labassay kits. Activities of hepatic GP and G6Pase were measured by glucose-6-phosphate dehydrogenase-coupled reaction. Real-time RT-PCR and Western blotting were used to determine the mRNA and protein levels of both enzymes. RESULTS: Geniposide (200 and 400 mg/kg) significantly decreased the blood glucose, insulin and TG levels in diabetic mice in a dose-dependent manner. This compound also decreased the expression of GP and G6Pase at mRNA and immunoreactive protein levels, as well as enzyme activity. CONCLUSION: Geniposide is an effective hypoglycemic agent in diabetic mice. The hypoglycemic effect of this compound may be mediated, at least in part, by inhibiting the GP and G6Pase activities.

Genipin inhibits endothelial exocytosis via nitric oxide in cultured human umbilical vein endothelial cells.

AIM: Exocytosis of endothelial Weibel-Palade bodies, which contain von Willebrand factor (VWF), P-selectin and other modulators, plays an important role in both inflammation and thrombosis. The present study investigates whether genipin, an aglycon of geniposide, inhibits endothelial exocytosis. METHODS: Human umbilical vein endothelial cells (HUVECs) were isolated from umbilical cords and cultured. The concentration of VWF in cell supernatants was measured using an ELISA Kit. P-selectin translocation on the cell surface was analyzed by cell surface ELISA. Cell viability was measured using a Cell Counting Kit-8. Mouse bleeding times were measured by amputating the tail tip. Western blot analysis was used to determine the amount of endothelial nitric oxide synthase (eNOS) and phospho-eNOS present. Nitric oxide (NO) was measured in the cell supernatants as nitrite using an NO Colorimetric Assay. RESULTS: Genipin inhibited thrombin-induced VWF release and P-selectin translocation in HUVECs in a dose- and time-dependent manner. The drug had no cytotoxic effect on the cells at the same doses that were able to inhibit exocytosis. The functional study that demonstrated that genipin inhibited exocytosis in vivo also showed that genipin prolonged the mouse bleeding time. Furthermore, genipin activated eNOS phosphorylation, promoted enzyme activation and increased NO production. L-NAME, an inhibitor of NOS, reversed the inhibitory effects of genipin on endothelial exocytosis. CONCLUSION: Genipin inhibits endothelial exocytosis in HUVECs. The mechanism by which this compound inhibits exocytosis may be related to its ability to stimulate eNOS activation and NO production. Our findings suggest a novel anti-inflammatory mechanism for genipin. This compound may represent a new treatment for inflammation and/or thrombosis in which excess endothelial exocytosis plays a pathophysiological role.

Ellagitannin (BJA3121), an anti-proliferative natural polyphenol compound, can regulate the expression of MiRNAs in HepG2 cancer cells.

MicroRNAs (miRNAs) play an important role in cancers. A number of miRNA expression-profiling studies have been done to identify the miRNA signatures of cancers from different cellular origin. There is, however, relatively little information on how anticancer agents regulate miRNA expression. Ellagitannin (BJA3121), 1,3-Di-O-galloyl-4,6-(s)-HHDP-b-D-glucopyranose, is a new natural polyphenol compound isolated from Balanophora Japonica MAKINO. Our preliminary results have shown that BJA3121 had antiproliferative effect and modified the expression of different genes in human HepG(2) cancer cells. In this study, we further evaluate whether this antineoplastic compound is able to alter miRNA expression in HepG(2) cells. We demonstrated for the first time that BJA3121 can regulate the expression of 25 miRNAs, including 17 upregulated and 8 downregulated miRNAs in HepG(2) cells. Our results suggested that BJA3121-modifed miRNA expression can mediate, at least in part, the antiproliferative and multigene regulatory action induced by the compound on HepG(2) cancer cells.

Synthesis, biological evaluation, and molecular docking investigation of 3-amidoindoles as potent tubulin polymerization inhibitors.

A series of novel 3-amidoindole derivatives possessing 3,4,5-trimethoxylphenyl groups were synthesized and evaluated for their antiproliferative and tubulin polymerization inhibitory activities. Some of them demonstrated moderate to potent activities in vitro against six cancer cell lines including MCF-7, MDA-MB-231, BT549, T47D, MDA-MB-468, and HS578T. The most active compound 27 inhibited the growth of T47D, BT549, and MDA-MB-231 cell lines with IC50 values at 0.04, 3.17, and 6.43 µM, respectively. Moreover, the flow cytometric analysis clearly revealed that compound 27 significantly inhibited growth of breast cancer cells through arresting cell cycle in G2/M phase via a concentration-dependent manner. In addition, the compound also exhibited the most potent anti-tubulin activity with IC50 values of 9.5 µM, which was remarkable, compared to CA-4. Furthermore, molecular docking analysis demonstrated the interaction of the compound 27 at the colchicine-binding site of tubulin. These preliminary results suggest that compound 27 is a very promising tubulin-binding agent and is worthy of further investigation aiming to the development of new potential anticancer agents.

Capsaicin-loaded folic acid-conjugated lipid nanoparticles for enhanced therapeutic efficacy in ovarian cancers.

In this study, folic acid-conjugated lipid nanoparticles were successfully prepared to enhance the active targeting of capsaicin (CAP) in ovarian cancers. The particles were nanosized and exhibited a controlled release of drug in the physiological conditions. The folic acid (FA)-conjugated system exhibited a remarkably higher uptake of nanoparticles in the cancer cells compared to that of non-targeted system. The folate-conjugated CAP-loaded lipid nanoparticles (CFLN) upon interacting with cancer cells were internalized via receptor-mediated endocytosis mechanism and resulted in higher concentration in the cancer cells. Consistently, CFLN showed a remarkably higher toxic effect compared to that of non-targeted nanoparticle system. CFLN showed significantly higher cancer cell apoptosis with nearly 39% of cells in apoptosis chamber (early and late) compared to only ∼21% and ∼11% for CAP-loaded lipid nanoparticles (CLN) and CAP. The loading of drug in the lipid nanoparticle system extended the drug retention in the blood circulation and allowed the active targeting to specific cancer cells. The prolonged circulation of drug attributed to the antifouling property of polyethylene glycol molecule in the structure. Overall, study highlights that using targeting moiety could enhance the therapeutic response of nanomedicines in the treatment of solid tumors.

[Purification of a new phospholipase A2 homologue from Agkistrodon blomhoffii siniticus and its effects on gene expression of Hep3B cells].

A new PLA2 homologue was purified from Agkistrodon blomhoffii Siniticus by applying reverse phase (HPLC) C18 column. The molecular weight of PLA2 homologue is 13900Da and its purity is 97.2%. The results of N-terminal sequence analysis were HLLQFRKMIKKMTKK. All the fragments were determined with the protein-protein BLAST software of GenBank. BLAST analysis showed that the N-terminal sequences of 15 amino acids were highly homologous with the sequences of other PLA2.

[Purification of a small peptide SV-PP-3 from the venom of Agkistrodon blomhoffii siniticus and its inhibition of platelet aggregation].

OBJECTIVE: To investigate the inhibitory effect of the small peptide SV-PP-3 from the venom of Agkistrodon blomhoffii siniticus on platelet aggregation. METHODS: The small peptide SV-PP-3 was isolated and purified by centrifugation at low temperature, sephadex G-75 column chromatography and reverse-phase (HPLC) on C-18 column. The platelet aggregation induced by adenosine diphosphate (ADP) was measured by LBY-NJ aggregometer. RESULTS: SV-PP-3 was purified from the venom of Agkistrodon blomhoffii siniticus, which inhibited the platelet ADP-induced platelet aggregation in a dose-dependent manner. CONCLUSION: SV-PP-3 can inhibit ADP-Induced platelet aggregation.

The cytotoxic effects of regorafenib in combination with protein kinase D inhibition in human colorectal cancer cells.

Metastatic colorectal cancer (mCRC) remains a major public health problem, and diagnosis of metastatic disease is usually associated with poor prognosis. The multi-kinase inhibitor regorafenib was approved in 2013 in the U.S. for the treatment of mCRC patients who progressed after standard therapies. However, the clinical efficacy of regorafenib is quite limited. One potential strategy to improve mCRC therapy is to combine agents that target key cellular signaling pathways, which may lead to synergistic enhancement of antitumor efficacy and overcome cellular drug resistance. Protein kinase D (PKD), a family of serine/threonine kinases, mediates key signaling pathways implicated in multiple cellular processes. Herein, we evaluated the combination of regorafenib with a PKD inhibitor in several human CRC cells. Using the Chou-Talalay model, the combination index values for this combination treatment demonstrated synergistic effects on inhibition of cell proliferation and clonal formation. This drug combination resulted in induction of apoptosis as determined by flow cytometry, increased PARP cleavage, and decreased activation of the anti-apoptotic protein HSP27. This combination also yielded enhanced inhibition of ERK, AKT, and NF-κB signaling. Taken together, PKD inhibition in combination with regorafenib appears to be a promising strategy for the treatment of mCRC.

[Immunological reaction between the peptides from S1 domain of SARS coronavirus S-protein and the serum from SARS patients].

OBJECTIVE: To examine the immunological reactions between the peptides of SARS coronavirus (SARS-Cov) S-protein and the serum of SARS patients for identifying the SARS-Cov epitope. METHODS: The peptides from S1 domain of SARS-Cov S-protein were synthesized by peptide synthesizer, and the immunological reaction of the peptides with the serum of SARS patients were examined by means of ELISA. RESULTS: The optical density value of the immunological reaction of synthesized 8 peptides with SARS patient serum was 1.5-2.6 times higher than that with normal serum. CONCLUSION: The 8 peptides from S1 domain of S protein appear to have low immunogenicity to the serum of SARS patients, indicating that these peptides may not be the epitope of the SARS-Cov.

Pyranocoumarins isolated from Peucedanum praeruptorum Dunn suppress lipopolysaccharide-induced inflammatory response in murine macrophages through inhibition of NF-κB and STAT3 activation.

Praeruptorin C, D, and E (PC, PD, and PE) are three pyranocoumarins isolated from the dried root of Peucedanum praeruptorum Dunn of Umbelliferae. In the present study, we investigated the anti-inflammatory effect of these compounds in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. Pyranocoumarins significantly inhibited LPS-induced production of nitric oxide, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). The mRNA and protein expressions of inducible nitric oxide synthase, IL-6, and TNF-α were also suppressed by these compounds. Both PD and PE exhibited greater anti-inflammatory activities than PC. Further study showed that pyranocoumarins suppressed the cytoplasmic loss of inhibitor κB-α protein and inhibited the translocation of NF-κB from cytoplasm to nucleus. In addition, pyranocoumarins suppressed LPS-induced STAT3 tyrosine phosphorylation. Taken together, the results suggest that pyranocoumarins may exert anti-inflammatory effects in LPS-stimulated RAW 264.7 macrophages through the inhibition of NF-κB and STAT3 activation.