Ratiometric electrochemical immunosensor for the detection of CA199 based on the ratios of NiCo@Fc-MWCNTs-LDH and 3D-rGOF@Ag/Au complexes.

Carbohydrate antigen 199 (CA199) is the most sensitive marker reported for pancreatic cancer, and it is a difficult task to develop a highly sensitive assay for CA199. During the experiment, a ratiometric electrochemical immunosensor for quantitative analysis of CA199 was prepared for NiCo@Fc-MWCNTs-LDH as the electrode sensing surface and 3D-rGOF@Ag/Au as the label of Ab2. NiCo@Fc-MWCNTs-LDH not only provide the required signal for the immunosensor, but also have a layered structure to obtain a large specific surface area, which can provide more sites for the placement of biological molecules. rGOF has the advantages of large specific surface area and high porosity, which can adsorb Ag electrochemical probe through redox reaction. The modification of gold nanoparticles can not only enhance the electrical conductivity of nano-composites, but also immobilize more biomolecules to improve the sensitivity of electrochemical sensors. With the beefing up of CA199 concentration, the oxidation peak current of Ag increases and the oxidation peak current of Fc-COOH decreases. The ratio (y = IAg/IFc-COOH) of two different signals was linear with the logarithm of CA199 concentration in a certain value range. Under optimal conditions, the immunosensor showed excellent performance in the concentration range of 0.0001 U/mL to 10 U/mL, and the detection limit was 5.55 × 10-4 U/mL. The strategy could clearly discriminate between matched and mismatched targets, demonstrating high specifificity. This approach further detects CA199 in human plasma to differentiate pancreatic cancer patients from healthy individuals with high accuracy. This method also provided a new idea for the ultrasensitive quantitative detection of other biomarkers.

The effects of stereotactic body radiotherapy on peripheral natural killer and CD3+CD56+ NKT-like cells in patients with hepatocellular carcinoma.

BACKGROUND: Both natural killer (NK) and CD3+CD56+natural killer T (NKT)-like cells play critical roles in the antitumor response. This study aimed to explore the effects of stereotactic body radiotherapy (SBRT) on peripheral NK and NKT-like cells in patients with hepatocellular carcinoma (HCC), and to identify possible surface markers on these cells that correlate with the prognosis. METHODS: Twenty-five HCC patients were prospectively enrolled in our study, and 10 healthy individuals were served as healthy controls. Flow cytometry was used to determine the counts and the percentages of peripheral NK and NKT-like cells, cells with certain receptors, and cells with intracellular interferon-γ and TNF-α secretion at different time points, including time points of prior to SBRT, at post-SBRT, and 3-month and 6-month after treatment. The Kaplan-Meier method with the log-rank test was applied for survival analysis. RESULTS: The peripheral NKT-like cells was increased at post-SBRT. Meanwhile, elevated levels of inhibitory receptors and reduced levels of activating receptors of NK cells were also observed in NK cells at post-SBRT, but the levels was not significantly different at 3-month and 6-month as compared with the baseline levels. Lower percentage of NKp30+NK cells before SBRT and higher percentage of CD158b+NK cells after SBRT were associated with poor progression-free survival. In addition, higher percentage of CD3+CD56+ NKT-like cells was associated with a higher overall survival rate in HCC patients. CONCLUSIONS: SBRT has an apparent effect on both peripheral NK and CD3+CD56+NKT-like cells. Lower percentage of NKp30+NK cells before SBRT and higher percentage of CD158b+NK cells after SBRT are correlated with poor patients' PFS. Higher percentage of CD3+CD56+ NKT-like cells is associated with higher OS in HCC patients.

Jinbei Oral Liquid ameliorates bleomycin-induced idiopathic pulmonary fibrosis in rats via reversion of Th1/Th2 shift.

Objective: Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal interstitial lung disease with high mortality. The pivotal role of Th1/Th2 immunological balance in the development and progression of IPF has been demonstrated previously. This study aimed to evaluate the effect of Jinbei Oral Liquid (JBOL) on IPF and its relationship with Th1/Th2 shift. Methods: Rats were divided into six groups: control group, model group (bleomycin), pirfenidone group (positive group, 54 mg/kg, i.g.) and JBOL (5.4, 10.8 and 21.6 mL/kg, i.g.) groups. The rat model was established by an intratracheal instillation of bleomycin (BLM, 5 mg/kg). One day after injection of BLM, pirfenidone or JBOL was given to rats once daily within 28 consecutive days, respectively. Positron emission tomography/computed tomography (PET/CT) was performed on the treated rats. The extent of alveolitis and fibrosis was observed by H&E and Masson trichrome staining. The contents of TGF-ß1, TNF-α, IL-4 and IFN-γ were further quantified by ELISA assay. Results: PET/CT and histopathological evidence showed the ability of JBOL to attenuate bleomycin-induced alveolitis and fibrosis extent, and the alveolitis lesion score was markedly decreased compared with the model group. The increased expression of inflammatory cytokines TGF-ß1 and TNF-α induced by bleomycin was also suppressed by JBOL. The Th1 response was limited by the reduced IFN-γ after BLM administration, and the Th2 response predominated significantly marked by the increased IL-4. JBOL could increase the level of IFN-γ and markedly increased the ratio of IFN-γ/IL-4. Conclusion: These findings suggested that JBOL may attenuate BLM-induced idiopathic pulmonary fibrosis via reducing inflammatory cell infiltration, pro-inflammatory cytokine release and excessive collagen deposition in rats. One of the mechanisms is the reversion of Th1/Th2 shift caused by BLM.

Inhibition of Sophocarpine on Poly I: C/D-GalN-Induced Immunological Liver Injury in Mice.

Increasing evidence has suggested that natural killer (NK) cells contribute to the pathogenesis of human immunological liver injury (ILI). Previous studies have demonstrated that Sophocarpine exerts activity in immune modulation. It also has a therapeutic effect on liver protection in that it can alleviate liver fibrosis by suppressing both the activation of hepatic stellate cells and the proliferation of the activated hepatic stellate cells. However, whether Sophocarpine protects the liver by regulating NK cell activity remains unclear. In this study, the modulating effect of Sophocarpine on NK cells in the liver was investigated. The results showed that Sophocarpine dramatically decreased the production of pro-inflammatory cytokines and attenuated the liver injury induced by Poly I: C/D-GalN in C57BL/6- mice. More importantly, Sophocarpine pre-treatment significantly suppressed NK cell activation and downregulated the expression of NKG2D, a receptor responsible for NK cell activation. Moreover, the protein levels of DAP12, ZAP76 and Syk decreased, as did their corresponding mRNA levels. Overall, our study demonstrates that Sophocarpine inhibits NK cell activity, thus making it a promising therapy for ILI.

[Research progress of Guanxin Danshen formula and its effective components in treating coronary artery heart disease].

Coronary artery heart disease (CHD) is one of the common cardiovascular diseases in clinical. The morbidity and mortality of CHD recently continue increasing in our country, which has aroused wide attention. Many studies confirm that traditional Chinese medicine has better therapeutic effect on CHD. Guanxin Danshen formula, widely used in the treatment of CHD, consists of Salviae Miltiorrhizae Radix et Rhizoma, Notoginseng Radix et Rhizoma and volatile oil from Dalbergiae Odoriferae Lignum, and has the efficacy in promoting blood circulation to resolve stasis, regulating the circulation of Qi and alleviating pain. This review summarized the pharmacologic effects and mechanism of Guanxin Danshen formula and its effective components in the treatment of CHD to provide reference for its fundamental research and clinical application.

Research progress of Guanxin Danshen formula and its effective components in treating coronary artery heart disease / 中国中药杂志

Coronary artery heart disease (CHD) is one of the common cardiovascular diseases in clinical. The morbidity and mortality of CHD recently continue increasing in our country, which has aroused wide attention. Many studies confirm that traditional Chinese medicine has better therapeutic effect on CHD. Guanxin Danshen formula, widely used in the treatment of CHD, consists of Salviae Miltiorrhizae Radix et Rhizoma, Notoginseng Radix et Rhizoma and volatile oil from Dalbergiae Odoriferae Lignum, and has the efficacy in promoting blood circulation to resolve stasis, regulating the circulation of Qi and alleviating pain. This review summarized the pharmacologic effects and mechanism of Guanxin Danshen formula and its effective components in the treatment of CHD to provide reference for its fundamental research and clinical application.

Effect of berberine on Escherichia coli, Bacillus subtilis, and their mixtures as determined by isothermal microcalorimetry.

The strong toxicity of pathogenic bacteria has resulted in high levels of morbidity and mortality in the general population. Developing effective antibacterial agents with high efficacy and long activity is in great demand. In this study, the microcalorimetric technique based on heat output of bacterial metabolism was applied to evaluate the effect of berberine on Escherichia coli, Bacillus subtilis, individually and in a mixture of both using a multi-channel microcalorimeter. The differences in shape of the power-time fingerprints and thermokinetic parameters of microorganism growth were compared. The results revealed that low concentration (20 µg/mL) of berberine began to inhibit the growth of E. coli and mixed microorganisms, while promoting the growth of B. subtilis; high concentration of berberine (over 100 µg/mL) inhibited B. subtilis. The endurance of E. coli to berberine was obviously lower than B. subtilis, and E. coli could decrease the endurance of B. subtilis to berberine. The sequence of half-inhibitory concentration (IC(50)) of berberine was: B. subtilis (952.37 µg/mL) > mixed microorganisms (682.47 µg/mL) > E. coli (581.69 µg/mL). Berberine might be a good selection of antibacterial agent used in the future. The microcalorimetric method should be strongly suggested in screening novel antibacterial agents for fighting against pathogenic bacteria.