Endogenous Adenosine 5'-Monophosphate, But Not Acetylcholine or Histamine, is Associated with Asthma Control, Quality of Life, and Exacerbations.

OBJECTIVE: Endogenous adenosine 5'-monophosphate (AMP), acetylcholine (ACh), and histamine (HA) are known to be important in bronchial contraction, but their clinical relevance to asthma is poorly understood. We aimed to quantify endogenous AMP, ACh, and HA in induced sputum samples and explore their relationships with asthma control and exacerbations. METHODS: 20 healthy subjects and 112 asthmatics underwent clinical assessment, sputum induction, and blood sampling. The level of asthma control was determined by the asthma control test (ACT) questionnaire. Asthma exacerbation was evaluated according to the criteria of the American Thoracic Society/European Respiratory Society. Levels of AMP, ACh, and HA in sputum were measured by liquid chromatography coupled to tandem mass spectrometry. IL-ß, IL-4, IL-5, IL-6, IL-8, IL-13, IL-17A, TNF-α, IFN-γ, and macrophage-derived chemokine (MDC) were also measured. RESULTS: Compared to healthy controls, asthmatics had higher levels of HA, lower levels of ACh, and similar levels of AMP in induced sputum samples. Compared to controlled asthma (n = 54), uncontrolled asthma (n = 58) showed higher AMP levels (P = 0.002), but similar HA and ACh levels. AMP was negatively correlated with ACT scores (r = - 0.348) and asthma quality of life questionnaire scores (r = - 0.188) and positively correlated with blood monocytes percentage (r = 0.195), sputum MDC (r = 0.214), and IL-6 levels (r = 0.196). Furthermore, AMP was associated with an increased risk of exacerbations in the preceding year. CONCLUSION: Endogenous AMP, but not ACh or HA, was associated with asthma control, quality of life, and exacerbations in the previous year, which indicates that AMP could be a clinically useful biomarker of asthma.

Application of Diffusion Kurtosis Imaging in Evaluating Acute Xerostomia in Nasopharyngeal Carcinoma Treated With Induction Chemotherapy Plus Concurrent Chemoradiotherapy.

Purpose: The aim of this study was to identify the efficacy of diffusion kurtosis imaging (DKI) in tracking and monitoring the dynamic change of parotid glands (PGs), submandibular glands (SMGs), sublingual glands (SLGs), and acute xerostomia in nasopharyngeal carcinoma (NPC) patients treated with induction chemotherapy (IC) plus concurrent chemoradiotherapy (CCRT). Methods: The prospective study recruited 42 participants treated with IC+CCRT. All patients underwent DKI scanning six times: before IC, before RT, in the middle of the RT course, immediately after RT, and 1 and 3 months post-RT. Mean diffusion coefficient (MD) and mean kurtosis (MK) of PG, SMG, SLG, saliva flow rate measured under resting (uSFR) and stimulated condition (sSFR), and xerostomia questionnaire (XQ) scores were recorded. Results: At each time point, sSFR was significantly higher than uSFR (p < 0.05 for all). MD of the salivary glands and XQ scores increased over time while MK, uSFR, and sSFR decreased. After IC, the significant differences were detected in MD and MK of bilateral SMG and MK of the left SLG (p < 0.05 for all), but not in MD and MK of PG, uSFR, sSFR, and XQ scores. After RT, sSFR at 1m-RT decreased significantly (p = 0.03) while no significant differences were detected in uSFR and XQ scores. Moderate-strong correlations were detected in ΔMD-PG-R%, ΔMK-PG-R%, ΔMD-PG-L%, ΔMK-PG-L%, ΔMD-SMG-R%, ΔMK-SMG-R%, ΔMD-SMG-L%, ΔMK-SMG-L%, and ΔMD-SLG-R%, with correlation coefficients (p < 0.05 for all) ranging from 0.401 to 0.714. ΔuSFR% was correlated with ΔMD-SMG% (p = 0.01, r = -0.39), ΔMD-SLG% (p < 0.001, r = -0.532), and ΔMK-SMG% (p < 0.001, r = -0.493). ΔsSFR% correlated with ΔMD-PG% (p = 0.001, r = -0.509), ΔMD-SMG% (p = 0.015, r = -0.221), and ΔMK-PG% (p < 0.001, r = 0.524). ΔXQ% was only correlated with ΔMK-PG% (p = 0.004, r = 0.433). Conclusion: DKI is a promising tool for tracking and monitoring the acute damage of PG, SMG, and SLG induced by IC+CCRT in NPC patients.

Sparing submandibular gland to alleviating acute xerostomia in patients with nasopharyngeal carcinoma treated with helical tomotherapy: Evaluation by diffusion kurtosis imaging.

PURPOSE: To identify the clinical significance of sparing submandibular glands (SMG) for the amelioration of acute xerostomia using diffusion kurtosis imaging (DKI) in nasopharyngeal carcinoma (NPC) patients treated with helical tomotherapy (HT). MATERIALS AND METHODS: The prospective study enrolled 42 participants treated with HT. All patients underwent five times of DKI scans before HT (pre-HT), in the middle of the HT course (mid-HT), immediately after HT (post-HT), and 1 months (1m-HT), 3 months post-HT(3m-HT). Mean diffusion (MD) and mean kurtosis (MK) of SMG, parotid glands (PG) and sublingual glands (SLG), saliva flow rate measures under resting (uSFR) and stimulated condition (sSFR), and xerostomia questionnaire scores (XQ) were recorded. Comparisons between the SMG-spared and -unspared groups were analyzed using two-factor repeated-measures ANOVA for the group as the inter-subject factor and the time as the intra-subject factor. RESULTS: When sparing SMG, the dose of spared-SMG and ipsilateral SLG was lower compared to that of unspared glands (p < 0.001). MD of spared-SMG and ipsilateral SLG in SMG-spared group were lower than that of SMG-unspared group (the simple effect for the group, p-value at mid-HT, post-HT, 1m- and 3m-HT was 0.014, 0.011, 0.000 and 0.000, respectively), MK of spared-SMG was higher conversely (the main effect for the group, p < 0.001), while uSFR and sSFR were significantly lower in SMG-unspared group (the main effect for the group, p = 0.002, and p = 0.045, respectively). No significant differences were detected in MK of SLG, MD/MK of PG, and XQ between the two groups (the main effect for the group, p values were 0.9, 0.37, 0.15, 0.86, respectively). There were significant differences in the effect of the time for all MD/MK of the salivary glands and for uSFR, sSFR, and XQ between the SMG-spared and -unspared groups (p values were all <0.001). CONCLUSION: Sparing SMG is of great clinical significance in alleviating acute xerostomia for NPC patients treated by helical tomotherapy as evaluated by diffusion kurtosis imaging and saliva flow rate.

Quality evaluation of bee pollens by chromatographic fingerprint and simultaneous determination of its major bioactive components.

Bee pollens constitute a large number of flavonoids and thus possess great medicinal value. However different varieties of bee pollen flavonoids vary with different species and their content also differ greatly in different region. Herein, the aim of present research is to establish a method based on high performance liquid chromatography (HPLC) for quantitative analysis of flavonoids compounds and chemical fingerprint analysis of bee pollen. Five batches of rape bee pollen collected from different region of China and particularly six bee pollen species obtained in Anhui were used to establish the fingerprint. The feasibility and advantages of the used HPLC fingerprint were verified for its similarity evaluation by systematically comparing chromatograms with professional analytical software. The similarities of liquid chromatography fingerprints for five batches of rape bee pollen were more than 0.994 while six batches of different species of bee pollen were lower than 0.810. In quantitative analysis, the six compounds showed good regression (R ≥ 0.9964) within the test ranges, and all the values for the RSD were lower than 2%. The developed HPLC fingerprint method was found simple, reliable, and it was validated for the quality control and identification of bee pollen. Additionally, simultaneous quantification of six flavonoids ingredients in the bee pollen samples was conducted to reveal the variation in their content. The results indicated that the HPLC fingerprint, as a characteristic distinguishing method combining similarity evaluation and quantification analysis, can be successfully used to assess the quality and also to identify the authenticity of bee pollen.

Protective effects of paeonol on inflammatory response in IL-1ß-induced human fibroblast-like synoviocytes and rheumatoid arthritis progression via modulating NF-κB pathway.

Various investigations have demonstrated that human fibroblast-like synoviocytes rheumatoid arthritis (HFLS-RA) take part in the chronic inflammatory responses and RA progression. Inhibition of synovium activation and inflammatory processes may represent a therapeutic target to alleviate RA. Paeonol, a major natural product, has many biological and pharmacological activities. However, its protective effects against RA considering HFLS-RA have not been explored. In this study, anti-inflammatory effects of paeonol were detected in interleukin-1ß (IL-1ß)-treated HFLS-RA. Our results demonstrated that paeonol had no effect on cell survival and IL-1ß-induced proliferation in HFLS-RA. Pretreatment with paeonol significantly suppressed the production of pro-inflammatory TNF-α, IL-6 and IL-1ß, and the expressions of matrix metalloproteinase-1/-3 in vitro and in vivo. Mice treated with paeonol (10 mg/kg) remarkablely attenuated arthritic symptoms based on clinical arthritis scores and histopathology in collagen-induced arthritis mice. Furthermore, the TLR4 expression and NF-κB p65 activation were inhibited by paeonol in vitro and in vivo. Our findings illustrated that paeonol had significantly suppressed inflammation effects in synovial tissues and RA progression. The potential mechanism might be based on the attenuation TLR4-NF-κB activation. These collective results indicated that paeonol might be a promising therapeutic agent for alleviating RA progress through inhibiting inflammations and NF-κB signalling pathway.

Protective effect of Rabdosia amethystoides (Benth) Hara extract on acute liver injury induced by Concanavalin A in mice through inhibition of TLR4-NF-κB signaling pathway.

Extract of Rabdosia amethystoides (Benth) Hara (ERA), a traditional Chinese medicine has antibacterial, antiviral, anti-tumor, anti-hepatitis and anti-inflammatory properties. However, the hepatoprotective effects and molecular mechanisms of ERA on acute liver injury have not been fully elucidated. This study aims to investigate the anti-inflammatory effect and liver protection of ERA against the acute liver injury induced by Concanavalin A (Con A) and its underlying molecular mechanisms in mice. Mice received ERA (50, 100, 150 mg/kg body weight) by gavage before Con A intravenous administration. We found that ERA pretreatment was able to significantly reduce the elevated serum alanine and aspartate aminotransferase levels and liver necrosis in Con A-induced hepatitis. In addition, ERA treatment significantly decreased the myeloperoxidase, malondialdehyde levels and augmented superoxide dismutase level in the liver tissue, and also suppressed the secretion of proinflammatory cytokines in the serum, compared with Con A group by enzyme linked immunosorbent assay. Furthermore, we observed that ERA pretreatment can significantly decrease the expression level of Toll-like receptor (TLR) 4 mRNA or protein in liver tissues. Further results showed that ERA pretreatment was capable of attenuating the activation of the NF-κB pathway by inhibiting IκBα kinase and p65 phosphorylation in Con A-induced liver injury. Our results demonstrate that ERA pretreatment has hepatoprotective property against Con A-induced liver injury through inhibition of inflammatory mediators in mice. The beneficial effect of ERA may be mediated by the downregulation of TLR4 expression and the inhibition of NF-κB activation.

Neuroprotective properties of aucubin in diabetic rats and diabetic encephalopathy rats.

In this study, we determined the neuroprotective effect of aucubin on diabetes and diabetic encephalopathy. With the exception of the control group, all rats received intraperitoneal injections of streptozotocin (STZ; 60 mg/kg) to induce type 1 diabetes mellitus (DM). Aucubin (1, 5, 10 mg/kg ip) was used after induction of DM (immediately) and diabetic encephalopathy (65 days after the induction of diabetes). The diabetic encephalopathy treatment groups were divided into short-term and long-term treatment groups. Treatment responses to all parameters were examined (body weight, plasma glucose, Y-maze error rates and proportion of apoptotic cells). In diabetic rats, aucubin controlled blood glucose levels effectively, prevented complications, and improved the quality of life of diabetic rats. In diabetic encephalopathy, aucubin significantly rescued neurons in the hippocampal CA1 subfield and reduced working errors during behavioral testing. The significant neuroprotective effect of aucubin could be seen not only in the short term (15 days) but also in the long term (45 days), which was a highly encouraging finding. These data suggest that aucubin may be a potential neuroprotective agent.