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Background: Re-Du-Ning injection (RDN) is a renowned heat-clearing traditional Chinese medicine for the treatment of respiratory diseases owing to its anti-inflammatory effects. However, very little is known about the pulmonary distribution and lung exposure–efficacy relationships. This study aimed to investigate the pulmonary distribution and biopharmaceutics concerning lung penetrability and affinity and the local anti-inflammatory effects after intravenous and pulmonary administration of RDN. Methods: Two iridoids and seven phenolic acid components were selected as the chemical markers in RDN. The in vitro pulmonary distribution and biopharmaceutics were conducted by evaluating the binding and disassociation kinetics of chemical markers in lung tissue explants whereas the in vivo evaluation was performed by determining the time-dependent concentrations of chemical markers in plasma, lung epithelial lining fluid (ELF), lung tissues and immune cells in the ELF after intratracheal and intravenous administrations of RDN. The inhibitory effects on tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) production were used to evaluate the anti-inflammatory effect of RDN on lung tissues in vitro and on mice with LPS-induced lung inflammation. Results: The chemical markers of RDN exhibited excellent lung penetrability but poor lung affinity in vitro and in vivo. After intravenous administration, the chemical markers appeared to rapidly penetrate through the lung tissue to reach the ELF, leading to markedly higher drug exposure to ELF and immune cells in the ELF than to lung tissues. Compared to intravenous injection, the intratracheal instillation of RDN increased drug exposure to lung tissue and immune cells in the ELF by up to > 80-fold, leading to improved anti-inflammatory potency and prolonged duration of action. Conclusion: The drug exposure to immune cells in the ELF was correlated with the lung-targeted anti-inflammatory effects of RDN and pulmonary delivery has the potential to replace intravenous injection of RDN for the treatment of respiratory diseases.

As the amount of data increases,correlates and crosses between data,the value of data needs to be maximized through data fusion.However,due to the complexity of the data fusion process,to clearly explain the data fusion process,it is necessary to establish a backtracking mechanism for data fusion.Although many researches are focused on data provenance,most of them are based on query and workflow,and few of them are for data fusion.This paper focuses on the provenance of data fusion,and proposes a method to support multi-granularity provenance.Firstly,the data fusion process is abstracted,and the semantic graphs of patterns,entities and attributes are constructed with the entity as the core,and an optimized model for storing storage provenance information is proposed.Secondly,on the basis of the semantic graph,the data provenance query algorithms at the entity level and the attribute level are proposed respectively,and the corresponding query optimization strategy are also proposed.Finally,experiments demonstrate the effectiveness of the proposed data provenance method.

Background: Chuankezhi injection (CKZ) is a traditional Chinese medicine for the treatment of respiratory diseases and has been often used off-label as a nebulization therapy. However, little is known about the aerosolization performance and pulmonary fate of the inhaled CKZ. This study aimed to evaluate the aerodynamic characteristics of nebulizer generated aerosols and to compare the properties of pharmacokinetics, lung distribution and anti-inflammation effects of CKZ after intratracheal and intravenous administration. Methods: The nebulization performance was evaluated in vitro based on the aerodynamic particle size distribution and aerosol output. The concentrations of epimedins A, B, C and icariin, the main active ingredients of CKZ, in plasma, bronchoalveolar lavage fluids (BALF) and lung tissues were measured by LC-MS/MS analysis. The pulmonary anti-inflammatory efficacy were tested using LPS-induced pulmonary inflammation mice model as indicated by the total cells counts, and the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in BALF. Results: The aerosols of CKZ generated by a commercial nebulizer showed excellent aerodynamic properties and delivery output. Following intratracheal instillation of CKZ, epidemins A, B and C, and icariin, were absorbed into the bloodstream with the mean absorption time varying from 101.8 min to 271.8 min, and their absolute bioavailabilities ranging from 26.4 % to 104 %. The instillation of CKZ increased the lung to plasma concentration ratios by 25.5–718 folds compared to intravenous administration, leading to improved and prolonged local anti-inflammatory effects. Conclusion: Nebulization therapy of CKZ could be a promising alternative to the injectable counterpart.

Background: Requirements of blood transfusions rise rapidly in China. Improving the efficiency of blood donation could help maintaining sufficient blood supplement. We conducted a pilot research to investigate the reliability and safety of collecting more units of red blood cell by apheresis. Methods: Thirty‐two healthy male volunteers were randomized into two groups: red blood cell apheresis (RA) (n = 16) and whole blood (WB) donation (n = 16). RA group donated individualized RBC volumes by apheresis according to the volunteers' basal total blood volumes and haematocrit levels, WB group donated 400 mL whole blood. All volunteers were scheduled seven visit times in 8 weeks' study period. The cardiovascular functions were assessed by laboratory examinations, echocardiography and cardiopulmonary functional tests. All results were compared between groups at the same visit time and compared between visit 1(before donation) and other visit times within the same group. Results: The average donated RBC volume in RA group and in WB group was 627.25 ± 109.74 mL and 175.28 ± 8.85 mL, respectively(p < 0.05); the RBC, haemoglobin and haematocrit levels changed significantly between times and between groups (p < 0.05). Cardiac biomarker levels such as NT‐proBNP, hs‐TnT and CK‐MB did not change significantly between times or between groups (p > 0.05). The echocardiographic and cardiopulmonary results did not change significantly between times or between groups during the whole study period(p > 0.05). Conclusions: We provided an efficient and secure method for RBC apheresis. By harvesting more RBC volumes at one single‐time, the cardiovascular functions did not change significantly compared with traditional whole blood donation. [ABSTRACT FROM AUTHOR]

Although the body has a strong immune system which can resists the invasion of leukemia cells, leukemia cells disseminate systemically and form an immunosuppressive microenvironment through a variety of mechanisms, including regulation of antigen presentation, utilization of immunosuppressive enzyme AXL, immune cell inhibitory checkpoint NKG2A and immunoregulatory gene VISTA , resulting in immune escape. Therefore, most types of leukemia are inevitable for the affliction of drug resistance or relapse, and the immune efficacy is not as significant as that of other hematological tumors and the prognosis is suboptimal. This article reviews the immune heterogeneity of leukemia microenvironment from many aspects, including anti-leukemia immunity and immune escape. In addition, it also reviews the latest progress and future prospects of immune checkpoint inhibition, adoptive cell therapy and vaccine therapy in leukemia, providing a theoretical basis for the development of personalized combination therapy strategies with less toxic side effects.

Objective: To investigate the effect and underlying mechanism of hispidulin on the proliferation and apoptosis of leukemia K562 cells., Methods: K562 cells were cultured in vitro and treated with 0, 5, 25 or 100 μmol/L hispidulin for 24 h. Cell proliferation and apoptosis were detected by CCK-8 and flow cytometry, respectively. Western blot was used to assess the expression of Bax, Bcl-2 and interleukin (IL)-37 proteins. Bone marrow mononuclear cells were extracted from 17 chronic myeloid leukemia patients and 21 healthy individuals by Ficoll-Hypaque density gradient method, and the expression of IL-37 protein was measured by Western blot. K562 cells with IL-37 overexpression or knockdown were constructed, and then treated with 0 or 100 μmol/L hispidulin for 24 h. Cell proliferation, apoptosis and protein expression of Bax and Bcl-2 were determined in the same way as above., Results: After K562 cells were treated with hispidulin, the cell inhibition rate, apoptosis rate, and the protein expression of Bax and IL-37 were significantly increased ( P <0.05), but the cell proliferation and expression of Bcl-2 protein were decreased ( P <0.05). The expression of IL-37 protein in bone marrow mononuclear cells of the leukemia patient was 0.24±0.03, which was significantly lower than 0.91±0.05 of healthy controls ( P <0.05). Overexpression of IL-37 significantly promoted inhibition rate, apoptosis rate, and expression of Bax protein in K562 cells ( P <0.05), but suppressed the expression of Bcl-2 protein ( P <0.05). In addition, knockdown of IL-37 could reverse the effects of hispidulin on proliferation and apoptosis of K562 cells., Conclusion: Hispidulin inhibits the proliferation and induces apoptosis of leukemia K562 cells, which may be related to the up-regulation of IL-37 protein in cells.

Background: Compounds that target tumor epigenetic events are likely to constitute a prominent strategy for anticancer treatment. Histone deacetylase inhibitors (HDACis) have been developed as prospective candidates in anticancer drug development, and currently, many of them are under clinical investigation. We assessed the anticancer efficacy of a now hydroxamate-based HDACi, YF-343, in triple-negative breast cancer development and studied its potential mechanisms., Methods: YF-343 was estimated as a novel HDACi by the HDACi drug screening kit. The biological effects of YF-343 in a panel of breast cancer cell lines were analyzed by Western blot and flow cytometry. YF-343 exhibited notable cytotoxicity, promoted apoptosis, and induced cell cycle arrest. Furthermore, it also induced autophagy, which plays a pro-survival role in breast cancer cells., Results: The combination of YF-343 with an autophagy inhibitor chloroquine (CQ) significantly suppressed breast tumor progression as compared to the YF-343 treatment alone both in vitro and in vivo . Mechanistically, the molecular mechanism of YF-343 on autophagy was elucidated by gene chip expression profiles, qPCR analysis, luciferase reporter gene assay, chromatin immunoprecipitation assays, immunohistochemical analysis, and other methods. E2F7, a transcription factor, promoted the expression of ATG2A via binding to the ATG2A promoter region and then induced autophagy in triple-negative breast cancer cells treated with YF-343., Conclusion: Our studies have illustrated the mechanisms for potential action of YF-343 on tumor growth in breast cancer models with pro-survival autophagy. The combination therapy of YF-343 and CQ maybe a promising strategy for breast cancer therapy., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

N6-methyladenosine (m6A) is one of the most common epigenetic modifications of eukaryotic mRNAs, which is involved in the regulation of gene expressions and biological processes in a variety of cells with dynamic and reversible methylation processes. In recent years, many studies have shown that m6A methylation modification not only acts on the growth, proliferation, and medullary differentiation of acute myeloid leukemia cells, but also participates in the regulation of the proliferation and apoptosis of other hematological tumor cells such as chronic myeloid leukemia and diffuse large B-cell lymphoma, and it can even weaken the efficacy of anti-hematological tumor immunotherapy and induce immune escape leading to tumor resistance. With the successive development of a variety of m6A methylation-related enzyme inhibitors, it will provide new therapeutic ideas for patients with relapsed and refractory hematological tumors. In this paper, we review the research progress on the mechanism of m6A methylation on the occurrence, development, and tumor immunity of various hematological tumors.