Scope
Quercetin (QU) is one of the most abundant flavonoids in plants and has attracted the attention of researchers because of its remarkable antirheumatoid arthritis (RA) effects and extremely low ...adverse reactions. However, the underlying mechanism needs further study.
Methods and results
Flow cytometry, immunofluorescence, enzyme linked immunosorbent assay （ELISA）, and quantitative real‐time polymerase chain reaction （qRT‐PCR） reveal the obvious inhibitory effects of QU on Th17 cell differentiation in arthritic mice. More importantly, QU markedly limits the development of Th17 cell polarization, which is virtually compromised by the treatment with peroxisome proliferator activated receptor γ (PPARγ) inhibitor GW9662 and knockdown of PPARγ. Additionally, molecular dynamics simulation and immunofluorescence exhibit QU directly binds to PPARγ and increases PPARγ nuclear translocation. Besides, QU confers its moderation effect on suppressor of cytokine signaling protein (SOCS3)/signal transducer and activator of transcription 3 (STAT3) axis partially depending on PPARγ. Furthermore, coimmunoprecipitation shows QU redistributes the corepressor silencing mediator for retinoid and thyroid‐hormone receptors (SMRT) from PPARγ to STAT3. Finally, the inhibition of Th17 response and the antiarthritic effect of QU are nullified by GW9662 treatment in arthritic mice.
Conclusion
QU targets PPARγ and consequently inhibits Th17 cell differentiation by dual inhibitory activity of STAT3 to exert antiarthritic effect. The findings facilitate its development and put forth a stage for uncovering the mechanism of other naturally occurring compounds with chemical structures similar to QU.
Quercetin is commonly found in foods with anti‐arthritic effects. In this work, authors try to explore the underlying mechanism of quercetin on rheumatoid arthritis. The research finds that quercetin could up‐regulate the expression of suppressors of cytokine signaling 3 (SCOS3) by directly activating peroxisome proliferator activated receptor γ (PPARγ), and further impede Th17 cell differentiation to alleviate arthritis.
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In the present study, the concentrations of lead (Pb), cadmium (Cd), arsenic (As), mercury (Hg), and copper (Cu) in 2245 batches of Chinese herbal medicines (CHMs) were measured using ...inductively coupled plasma-mass spectroscopy (ICP-MS). We developed a risk assessment strategy that assessed the heavy metal-associated health risk of CHMs based on our large dataset. Using a combination of the mean and 95th percentile (P95) values of the chronic daily intake (CDI), hazard quotient (HQ), hazard index (HI), and lifetime cancer risk (CR), the health risks of the average exposure population and the high exposure population were estimated, respectively. To obtain a precise and realistic risk assessment, the exposure frequency and exposure duration were determined using questionnaire data from 20,917 randomly selected volunteers. Additionally, given the specific ingestion characteristics of CHMs, the safety factor and the transfer rates of heavy metals were highlighted as well. The concentrations of Pb, Cd, As, Hg, and Cu in 2245 batches of CHMs were 1.566, 0.299, 0.391, 0.074, and 8.386 mg/kg, respectively. The mean HI values indicated that consumption of most CHMs would not pose an unacceptable health risk to the average exposure population, except for argy wormwood leaf (1.326), morinda root (2.095), plantain herb (1.540), chrysanthemum flower (1.146), and Indian madder root (2.826). In addition, CR assessment for Pb and As revealed that, for the average exposure population, the risk of developing cancers was lower than the acceptable levels (1 × 10−4) in the clinic. However, the P95 of the HI and CR values indicated that more attention should be paid to the systemic effects of CHMs in terms of both non-carcinogenic and carcinogenic health risks for the high exposure population. Furthermore, in order to serve population health better, national and international guidelines have now been established. The risk assessment strategy developed in this study is the first of its kind, and contributed to the risk assessment, guidelines, and safety standards for heavy metals in CHMs.
Objective: To observe the anti-proliferation and radiosensitization effect of chitooligosaccharides(COS) on human lung cancer cell line Hep G2. Methods: CCK-8 assay was employed to obtain the ...inhibition ratio of COS on Hep G2 cells at 24 h after treatment. The clonogenic assay was used to analyze the cell viability of RAY group and RAY+COS group with X-ray of 0, 1, 2, 4, 6 and 8 Gy, and the cell survival curve was used to analyze the sensitization ratio of COS. Flow cytometry was employed to detect cell cycle and apoptosis rate in control group, RAY group and RAY+COS group after 24 h treatment. Results: COS inhibited the proliferation of Hep G2 cells, and the inhibition rate positively correlated with the concentration of COS. The cell viability decreased with increasing exposure dose in RAY group and RAY+COS group. The cell viabilities of RAY+COS group were lower than those of RAY group at the dose of 4, 6 and 8 Gy(P<0.05), and the sensitization ratio of COS was 1.19. There were higher percentage at G2/M phase and apoptosis rate, and lower percentage at S phase in RAY+COS group versus the other two groups(P<0.01). Conclusions: COS can inhibit the proliferation of Hep G2 cells, and enhance the radiosensitization of Hep G2 cells, induce apoptosis and G2/M phase arrest.
This study was to observe the neurological protective effects of astragalosides (AST) on focal cerebral ischemia-reperfusion (I/R) injury in rats and to explore its possible mechanism. Male SD rats ...received right middle cerebral artery occlusion for 120 min and AST (40 mg/kg) was orally administered. The rats were decapitated 1, 3, 7, and 14 days after reperfusion. The neurological deficit score, infarct volume and water content of brain were measured; the activity of superoxide dismutase (SOD), lactate dehydrogenase (LDH) and nitric oxide synthase (NOS), and the content of malondialdehyde (MDA), lactate (LD) and nitric oxide (NO) of brain tissue were detected too. The expression of inducible nitric synthase (iNOS), nerve growth factor (NGF) and tropomyosin receptor kinase A (TrkA) mRNA were measured by RT-PCR or real-time PCR. AST could significantly reduce the neurological deficit score; infract volume and water content, increase SOD and LDH activities, decrease NOS activity and MDA, LD and NO content. AST treatment could down-regulate expression of iNOS mRNA, while, NGF and TrkA mRNA were up-regulated. Our data suggest that AST have the protective effects on focal cerebral ischemia in rats at the different reperfusion time points, the mechanism may be related to the antioxidation, regulated the expressions of iNOS, NGF and TrkA mRNA.
Abstract Several approaches are being taken worldwide to develop vaccines against H5N1 viruses; most of them, however, pose both practical and immunological challenges. One potential strategy for ...improving the immunogenicity of vaccines involves the use of alphavirus replicons and VP22, a herpes simplex type 1 (HSV-1) protein. In this study, we analysed the antigenic peptides and homogeneity of the HA sequences (human isolates of the H5N1 subtype, from 1997 to 2003) and explored a novel alphavirus replicon system of VP22 fused with HA, to assess whether the immunogenicity of an HA-based replicon vaccine could be induced and augmented via fusion with VP22. Further, replicon particles expressing VP22, and enhanced green fluorescent protein (EGFP) were individually used as controls. Cellular immune responses in mice immunised with replicons were evaluated by identifying specific intracellular cytokine production with flow cytometry (FCM). Animal-based experimentation indicated that both the IL-4 expression of CD4+ T cells and the IFN-γ expression of CD8+ T cells were significantly increased in mice immunised with VPR-HA and VPR-VP22/HA. A dose titration effect vis-à-vis both IL-4 expression and IFN-γ expression were observed in VPR-HA- and VPR-VP22/HA-vaccinated mice. Our results revealed that both VPR-VP22/HA and VPR-HA replicon particles presented a promising approach for developing vaccines against human-avian influenza, and VP22 could enhance the immunogenicity of the HA antigens to which it is fused.
To study the effect of astragalosides (AST) on the anoxia/reoxygenation (A/R) injured neuron in rat.
Primary cultured rat's hippocampal neurons were made into A/R model cells. The cell viability was ...detected by MTT assay and lactate dehydrogenase releasing methods; the activity of superoxide dismutase (SOD), and contents of malondialdehyde (MDA) and nitride oxide (NO) in culture supernate were detected; the apoptosis rate of hippocampal neurons after A/R was measured by flow cytometry with double-staining of Hoechst33258 and AnnexinV-PI; and intracellular calcium ion Ca2+i was observed with a cofocal laser-scanning microscope and determined by fluorescent probe Fluo-3/AM.
AST enhanced the cell viability of neurons after A/R injury, increased SOD activity and decreased the MDA and NO contents in supernate, reduced the A/R-induced apoptosis and decreased the calcium overload in neurons.
AST has the protective effects on A/R injured neurons, the mechanism is possibly related with its anti-oxidation and calcium
Alphavirus replicons, in which structural protein genes are replaced by heterologous genes, express high levels of the heterologous proteins. On the basis of the potencies of replicons to ...self-replicate and express foreign proteins and the remarkable intercellular transport property of VP22, a novel alphavirus Semliki Forest virus (SFV) replicon system of VP22 fused with a model antigen, hemagglutinin (HA), of the human-avian H5N1 influenza virus, was explored in this study. Further, replicon particles expressing HA, VP22, and enhanced green fluorescent protein (EGFP) individually were used as controls. By flow cytometry based on the analysis of transfection efficiency, SFV-EGFP replicon particle titer was 1.13
×
10
7
transducing units (TU)/ml. The titers of SFV-HA, SFV-VP22 and SFV-VP22-HA replicon particles, which were titrated by using SFV-EGFP replicon particles, were 1.42
×
10
7, 3.23
×
10
7, and 1.01
×
10
7
TU/ml, respectively. HA and VP22-HA expression was observed in SFV-HA- and SFV-VP22-HA-transfected BHK-21 cells, respectively. Immunofluorescence staining revealed that the fluorescence intensity in the SFV-VP22-HA-transfected BHK-21 cells was more than that in the SFV-HA-transfected BHK-21 cells. Both SFV-VP22-HA and SFV-HA replicon particles presented a promising approach for developing vaccines against human-avian influenza. VP22-HA fusion protein with similar trafficking properties may also enhance vaccine potency.
DNA modifications such as 5-methylcytosine （5mC） and 5-hydroxymethylcytosine （5hmC） are epigenetic marks known to affect global gene efpression in mammals. Given their prevalence in the human genome, ...close correlation with gene expression and high chemical stability, these DNA epigenetic marks could serve as ideal biomarkers for cancer diagnosis. Taking advantage of a highly sensitive and selective chemical labeling technology, we report here the genome-wide profiling of 5hmC in circulating cell-free DNA （cfDNA） and in genomic DNA （gDNA） of paired tumor and adjacent tissues collected from a cohort of 260 patients recently diagnosed with colorectal, gastric, pancreatic, liv- er or thyroid cancer and normal tissues from 90 healthy individuals. 5hmC was mainly distributed in transcriptionally active regions coincident with open chromatin and permissive histone modifications. Robust cancer-associated 5hmC signatures were identified in cfDNA that were characteristic for specific cancer types. 5hmC-based biomarkers of cir- culating cfDNA were highly predictive of colorectal and gastric cancers and were superior to conventional biomarkers and comparable to 5hmC biomarkers from tissue biopsies. Thus, this new strategy could lead to the development of effective, minimally invasive methods for diagnosis and prognosis of cancer from the analyses of blood samples.
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