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Introduction: Loratadine (LOR) (Fig. 1), an active H1 receptor antagonist, is often used in the treatment of allergic disorders such as seasonal allergies and skin rash [1]. LOR was clinically approved for symptomatic relief of nasal and non-nasal symptoms of allergic rhinitis in children ≥2years. Materials and Methods: An adapted method of liquid chromatography-mass spectrometry (LC/MS/MS) was developed and validated to measure the concentrations of loratadine (LOR) and its active metabolite descarboethoxyloratadine (DCL) from pediatric plasma. After being mixed with the internal standard (IS, propranolol) and precipitated with methanol, samples were centrifuged and 20 μL of the supernatants were injected into the HPLC system. Separation was carried out on a reversed-phase C18 gradient column using a mobile phase consisting of water (containing 0.1 % formic acid) and acetonitrile. The flow rate was 0.5 mL/min and the running time was 5.0 min for each sample. Results and Conclusion: Quantitation of LOR, DCL and IS was performed using MRM mode and the transitions were: 383.1 → 337.1 for LOR, 311.1 → 259.0 for DCL and 260.2 → 116.0 for propranolol, respectively. The method was validated according to FDA guidelines, precisions and accuracies met the requirements in all cases. Calibration curves were 0.2–50.0 ng/mL for both LOR and DCL. This method was then applied for a pilot study examining the pharmacokinetics and therapeutic drug monitoring of LOR in children.

Sesquiterpenoids are a major type of compound found in Solanum lyratum (S. lyratum). The present study aimed to investigate whether sesquiterpenoids from S. lyratum demonstrated cytotoxicity against the MCF-7, HCT-8, A-549, SGC-7901 and BEL-7402 cell lines, and the mechanism of solajiangxin H and lyratol D, which exhibited high cytotoxicity against SGC-7901 cells (half maximal inhibitory concentration, IC50=4.8 and 5.9 µg/ml), was associated with mitochondria-mediated apoptosis. The results of the Cell Counting Kit-8 assay indicated that 15 sesquiterpenoids had cytotoxicity against the aforementioned cultured cells. The results of DAPI staining and western blot analysis, used to study the anticancer mechanisms of solajiangxin H and lyratol D in SGC-7901 cells, suggested that solajiangxin H and lyratol D induced the apoptosis of SGC-7901 cells significantly (P

Objective. Coronary heart disease (CHD) has been regarded as a serious and common disease in the modern society. This study aims to investigate the effect of Granule of BU-XIN RUAN-MAI (BXRM) on angina pectoris of coronary heart disease and to explore the molecular mechanisms underlying Granule of BU-XIN RUAN-MAI-mediated protective activity against this disease. Methods. The effects of Granule of BU-XIN RUAN-MAI on clinical symptoms of patients’ angina were indicated by hemorheology indicators including high shear of blood viscosity, low shear of blood viscosity, plasma viscosity, erythrocyte rigidity index, D-D dimer, fibrinogen content, and lipid content. The effects of Granule of BU-XIN RUAN-MAI on isoprenaline-induced myocardial cell injury were determined by conducting H&E staining and by performing ELISA to examine the serum content of MDA, SOD, Na+/K+-ATPase, cAMP, and the content of inflammatory factors in isoprenaline-induced rats. Meanwhile, western blot and real time PCR were used to determine the expression of genes involved in oxidation and energy metabolism, and real time PCR was also used for determination of miR-542-3p expression. Luciferase reporter assay was conducted to test the binding sites of miR-542-3p on GABARAP 3′UTR. The chemical compositions of Granule of BU-XIN RUAN-MAI were determined by liquid LC-QTOF-MS. Results. Granule of BU-XIN RUAN-MAI significantly attenuated the clinical symptoms of patients’ angina by improving the patients’ heart rate and by decreasing the level of hemorheology indicators and also by reducing the serum content of TC, TG, LDL, and elevated HDL content. H&E staining demonstrated that Granule of BU-XIN RUAN-MAI ameliorated the myocardial ischemia in a dose-dependent manner. Besides, Granule of BU-XIN RUAN-MAI downregulated serum MDA content and upregulated the content of SOD, Na+/K+-ATPase, and cAMP in isoprenaline-induced rats. Granule of BU-XIN RUAN-MAI significantly improved oxidation stress by increasing PPARα expression, and it inhibited inflammation by downregulating expression and contents of IL-6, IL-1β, and TNF-α. Then, Granule of BU-XIN RUAN-MAI-containing serum increased the SOD content, and reduced the MDA content in angiotensin II-stimulated HUVEC cells. The granule of BU-XIN RUAN-MAI-containing serum obviously downregulated protein expressions of P40phox, P47phox, and P67phox in plasma membrane, and it significantly increased protein levels of P40phox, P47phox, and P67phox in the cytoplasm of HUVEC cells. Furthermore, GABARAP was reduced in heart tissues of ISO-induced rats and in angiotensin II-stimulated cell lines, and GABARAP was required for the inhibitory activity of Granule of BU-XIN RUAN-MAI on oxidation and inflammation in vivo and in vivo. GABARAP could be upregulated by Granule of BU-XIN RUAN-MAI by inhibiting the expression of miR-542-3p, which may significantly enhance oxidation and inflammation by targeting GABARAP in cardiomyocytes. Moreover, the silencing of GABARAP could obviously reverse the granule of BU-XIN RUAN-MAI-mediated protective activity against coronary heart disease, and interfering GABARAP expression also could partly block the anti-miR-542-3p-controlled oxidation and inflammation in cardiomyocytes. Besides, salidroside, loganin, and polydatin were the main compounds of granules of BU-XIN RUAN-MAI. Conclusion. Granule of BU-XIN RUAN-MAI is an excellent prescription for treatment of coronary heart disease by suppressing inflammation and NAPDH-mediated oxidative stress. The miR-542-3p/GABARAP axis is required for Granule of BU-XIN RUAN-MAI, exhibiting its protective activity against the pectoris of coronary heart disease.

Introduction. Hypertensive renal damage is a chronic and life-threatening kidney disease all over the world. The traditional Chinese medicine Jiang Ya Yi Shen (JYYS) granule has been a perfect drug for patients with hypertensive renal injury in clinic for 20 years in China. However, the molecular mechanism of JYYS granule remains unknown in treatment of this disease. Methods. The clinic data were from this study’s patients. The clinical symptoms of patients were indicated by (N-Acetyl-β-D-Glucosaminidase) NAG, (albumin) Alb, and (β2-microglobin) β2-MG content in urinary of patients, and renal artery’s hemodynamic parameters including (pulse index) PI, mean velocity of the arterial blood (Vm), minimum velocity of the diastolic stage (Vdmin) and peak velocity of the systolic wave (Vsmax). To further observe the effect of JYYS granule on renal damage, the rats were included in six groups: normal rats (WKY), spontaneously hypertensive rats (SHR), positive drug-treated rats (Benazepril), low dose JYYS (L), middle dose JYYS (M), and high dose JYYS (H). Then, we observed the effect of JYYS on renal function, renal tubules, inflammatory cell infiltration, and small artery thickening, and we explored the potential mechanism of JYYS in treatment of renal injury. Results. JYYS significantly improved the clinic symptoms of patients with hypertensive nephropathy by downregulating NAG, Alb, and β2-MG content in urinary of patients and by decreasing renal artery’s hemodynamic parameters including PI, Vm, Vdmin, and Vsmax. In SHR, JYYS significantly improved renal function including creatinine clearance rate, urinary albumin/creatinine, β2-MG/creatinine and arteria caudalis pressure in SHR. Secondly, light and electron microscopic examinations told that after administration of JYYS and Benazepril, the mesangial region exhibited no hyperplasia and renal capsule did not expanded, and there no abnormalities were observed in renal tubules, inflammatory cell infiltration and small artery thickening in SHR. Thirdly, JYYS exhibited its protective role by inhibiting nuclear factor kappa beta signaling-mediated micro-inflammation cytokines including interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), intercellular cell adhesion molecule-1 (ICAM-1), and monocyte chemotactic protein 1 (MCP-1) in SHR. Conclusion. JYYS is a promising prescription of Chinese medicine for patients with hypertension and hypertensive renal damage.

Mounting evidence has strongly implicated oxidative stress in the development of cardiac dysfunction, and myocardial apoptosis contributes to the pathogenesis of heart failure. Quantitative cardiac proteomics data revealed that pressure load by TAC resulted in a significant decline in mitochondrial metabolic activity, where TIIA (Tanshinone IIA sulfonate) treatment reversed it in vivo, which might be mediated by Nrf2. In NRVMs, TIIA treatment ameliorated H2O2-induced caspase-3/9 activations through the suppression of p38 and mTOR signaling pathways, where caspase-mediated cleavage of YY1 and PARP resulted in the defects in mitochondrial biogenesis and DNA repair, and this event finally led to cardiomyocyte apoptosis. Mass spectrometry analysis showed that TIIA hydrophobically interacted with Keap1 (the cytoplasmic repressor of Nrf2) and induced its degradation in vitro. Site-directed mutagenesis of Keap1 identified V122/V123/I125 to be the critical residues for the TIIA-induced de-dimerization and degradation of Keap1. Besides, TIIA treatment also epigenetically up-regulated Nrf2 gene transcription, where it hypomethylated the first 5 CpGs of Nrf2 promoter. Furthermore, cardiac-specific Nrf2 knockout mice exhibited the significantly dampened anti-apoptotic effects of TIIA.

Severe burn shock remains an unresolved clinical problem with an urgent need to explore novel therapeutic treatments. Intracellular β-catenin, through interaction with other proteins, has been reported to be able to regulate the size of cutaneous wounds. Higher expression of β-catenin is associated with larger sized wounds. However, the identification of serum β-catenin complex is difficult and has been rarely reported. The exploitation of more binding partners can contribute to uncovering the exact mechanisms behind serum β-catenin mediated biological effects. Here, we describe a method that consists of immunoprecipitation, SDS-PAGE, in-gel digestion, and nanoLC coupled to LCMS-IT-TOF for the investigation of serum β-catenin complex in mice scald model. Among selected gel bands obtained from the protein gels, a total of 31 peptides were identified and sequenced with high statistical significance (p

Hydrothermal reactions of benzene-1,3,5-triyltris(methylene)triphosphonic acid (H6L1) or (2,4,6-trimethylbenzene-1,3,5-triyl)tris(methylene)triphosphonic acid (H6L2) with metal sulfates, 4,4′-bipyridyl (4,4′-bipy), 2,2′-bipyridyl (2,2′-bipy), 1,10-phenanthroline (1,10-phen) and 1,2-di(4-pyridyl)ethylene (dpe), afforded eight new transition metal trisphosphonates, namely, [Cu2(H3L1)2(H2O)2][H2dpe][H2O]4 (1), [Ni1.5(H3L2)(H2O)2][H2O] (2), [Ni(H4L2)(1,10-phen)(H2O)2] (3), [Ni(H4L2)(2,2′-bipy)(H2O)2] (4), [Cu(H4L2)(4,4′-bipy)] (5), [Cu(H4L2)(1,10-phen)][H2O] (6), [Cu(H4L2)(2,2′-bipy)(H2O)][H2O]0.13 (7), and [Mn1.5(H3L2)(H2O)2][H2O]1.1 (8). The single-crystal X-ray diffraction measurements indicate that compounds 2 and 8 are isostructural and feature 3D framework structures with (5,6,8)-net topology; 1, 5 and 6 exhibit 2D layered structures; whereas 3, 4 and 7 have 0D dimer structures. The trisphosphonate ligands (H6L1 and H6L2) in these eight compounds adopt either cis–cis–cis or cis–trans–trans conformation with or without the existence of an auxiliary N-containing ligand. The attachment of methyl groups to the benzene core can enhance the crystallinity and enrich the structure diversity. The introduction of 2,2′-bipy and 1,10-phen usually result in low dimensionality whereas 4,4′-bipy can extend the structure to a higher dimensionality. The activated sample of compound 5 has a permanent 1D nanoporous structure and shows high selective adsorption of CO2 over CH4.