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Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, characterized by the loss or low expression of estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2) and progesterone receptor (PR). Due to the lack of clear therapeutic targets, paclitaxel (PTX) is often used as a first-line standard chemotherapy drug for the treatment of high-risk and locally advanced TNBC. PTX is a diterpenoid alkaloid extracted and purified from Taxus plants, functioning as an anticancer agent by inducing and promoting tubulin polymerization, inhibiting spindle formation in cancer cells, and preventing mitosis. However, its clinical application is limited by low solubility and high toxicity. Nanodrug delivery system (NDDS) is one of the feasible methods to improve the water solubility of PTX and reduce side effects. In this review, we summarize the latest advancements in PTX-targeted NDDS, as well as its combination with other codelivery therapies for TNBC treatment. NDDS includes passive targeting, active targeting, stimuli-responsive, codelivery, and multimode strategies. These systems have good prospects in improving the bioavailability of PTX, enhancing tumor targeting, reducing toxicity, controlling drug release, and reverse tumor multidrug resistance (MDR). This review provides valuable insights into the clinical development and application of PTX-targeted NDDS in the treatment of TNBC.

BackgroundPueraria montana var. lobata (Willd.) Maesen & S.M.Almeida ex Sanjappa & Predeep (syn. Pueraria lobata (Willd.) Ohwi) and Schisandra sphenanthera Rehder & E.H. Wilson are traditional edible and medicinal hepatoprotective botanical drugs. Studies have shown that the combination of two botanical drugs enhanced the effects of treating acute liver injury (ALI), but the synergistic effect and its action mechanisms remain unclear. This study aimed to investigate the synergistic effect and its mechanism of the combination of Pueraria montana var. lobata (Willd.) Maesen & S.M.Almeida ex Sanjappa & Predeep (syn. Pueraria lobata (Willd.) Ohwi) (PM) and Schisandra sphenanthera Rehder & E.H. Wilson (SS) in the treatment of ALI.MethodsHigh performance liquid chromatography (HPLC) were utilized to conduct the chemical interaction analysis. Then the synergistic effects of botanical hybrid preparation of PM-SS (BHP PM-SS) against ALI were comprehensively evaluated by the CCl4 induced ALI mice model. Afterwards, symptom-oriented network pharmacology, transcriptomics and metabolomics were applied to reveal the underlying mechanism of action. Finally, the key target genes were experimentally by RT-qPCR.ResultsChemical analysis and pharmacodynamic experiments revealed that BHP PM-SS was superior to the single botanical drug, especially at 2:3 ratio, with a better dissolution rate of active ingredients and synergistic anti-ALI effect. Integrated symptom-oriented network pharmacology combined with transcriptomics and metabolomics analyses showed that the active ingredients of BHP PM-SS could regulate Glutathione metabolism, Pyrimidine metabolism, Arginine biosynthesis and Amino acid sugar and nucleotide sugar metabolism, by acting on the targets of AKT1, TNF, EGFR, JUN, HSP90AA1 and STAT3, which could be responsible for the PI3K-AKT signaling pathway, MAPK signaling pathway and Pathway in cancer to against ALI.ConclusionOur study has provided compelling evidence for the synergistic effect and its mechanism of the combination of BHP PM-SS, and has contributed to the development and utilization of BHP PM-SS dietary supplements.

Abstract Norcantharidin (NCTD) is a demethylated derivative of cantharidin (CTD), the main anticancer active ingredient isolated from traditional Chinese medicine Mylabris. NCTD has been approved by the State Food and Drug Administration for the treatment of various solid tumors, especially liver cancer. Although NCTD greatly reduces the toxicity of CTD, there is still a certain degree of urinary toxicity and organ toxicity, and the poor solubility, short half-life, fast metabolism, as well as high venous irritation and weak tumor targeting ability limit its widespread application in the clinic. To reduce its toxicity and improve its efficacy, design of targeted drug delivery systems based on biomaterials and nanomaterials is one of the most feasible strategies. Therefore, this review focused on the studies of targeted drug delivery systems combined with NCTD in recent years, including passive and active targeted drug delivery systems, and physicochemical targeted drug delivery systems for improving drug bioavailability and enhancing its efficacy, as well as increasing drug targeting ability and reducing its adverse effects. Graphical Abstract

Abstract Urokinase-type plasminogen activator receptor (uPAR) is an attractive target for the treatment of cancer, because it is expressed at low levels in healthy tissues but at high levels in malignant tumours. uPAR is closely related to the invasion and metastasis of malignant tumours, plays important roles in the degradation of extracellular matrix (ECM), tumour angiogenesis, cell proliferation and apoptosis, and is associated with the multidrug resistance (MDR) of tumour cells, which has important guiding significance for the judgement of tumor malignancy and prognosis. Several uPAR-targeted antitumour therapeutic agents have been developed to suppress tumour growth, metastatic processes and drug resistance. Here, we review the recent advances in the development of uPAR-targeted antitumor therapeutic strategies, including nanoplatforms carrying therapeutic agents, photodynamic therapy (PDT)/photothermal therapy (PTT) platforms, oncolytic virotherapy, gene therapy technologies, monoclonal antibody therapy and tumour immunotherapy, to promote the translation of these therapeutic agents to clinical applications.

Abstract Functioning as miRNA sponges, long non-coding RNA (lncRNA) exert its pharmacological action via regulating expression of protein-coding genes. However, the lncRNA-mediated ceRNA in cerebral Infarction (CI) remains unclear. In this study, the expression recordsets of mRNA, lncRNA and miRNA of CI samples were obtained from the NCBI GEO datasets separately. The differentially expressed lncRNAs (DELs), miRNAs (DEMis) and mRNAs (DEMs) were identified by limma package in R platform. A total of 267 DELs, 26 DEMis, and 760 DEMs were identified as differentially expressed profiles, with which we constructed the ceRNA network composed of DELs-DEMis-DEMs. Further, clusterProfiler package in R platform is employed for performing Gene Ontology (GO) and KEGG pathway analysis. An aberrant ceRNA network was constructed according to node degrees in CI, including 28 DELs, 19 DEMs and 12 DEMis, from which we extracted the core network, in which 9 nodes were recognized as kernel genes including Tspan3, Eif4a2, rno-miR-208a-3p, rno-miR-194-5p, Pdpn, H3f3b, Stat3, Cd63 and Sdc4. Finally, with the DELs-DEMis-DEMs ceRNA network provided above, we can improve our understanding of the pathogenesis of CI mediated by lncRNA.

Background. Osteoarthritis (OA) is a common degenerative disease of bone and joint characterized by the damage of articular cartilage and hypertonia, which often occurs in the middle-aged and elderly. Traditional Chinese medicine (TCM) therapy, including acupuncture (ACU), oral administration, and external use of traditional Chinese medicines (TCMs), can significantly improve the therapeutic effect on OA and reduce the occurrence of side effects. We provide a latest meta-analysis on the treatment of OA with TCM. Materials and Methods. In the electronic database, appropriate articles without language restrictions on keywords were selected until August 1, 2019. All trajectories are screened according to certain criteria. The quality of qualified research was also assessed. We have made a detailed record of the results of the measurement. Meta-analysis was carried out with Revman 5.3 software. Results. Forty-four articles involving 4014 patients (2012 cases in the experimental group and 2002 cases in the control group) with OA were selected. This article focuses on the study of the treatment of OA by using the general mode of TCM. The quality evaluation included in the study was evaluated independently according to the Cochrane intervention system evaluation manual. In this meta-analysis, 68.18% of the literature correctly described the conditions for the generation of random assignment sequences, only 6.82% of the literature correctly mentioned the hidden details of allocation, and all studies mentioned randomly assigned participants. Compared with Western medicine, the total effective rate (TER) of OA treatment in TCM was significantly increased and the recurrence rate (RR) was significantly decreased (P

Background: Percutaneous coronary intervention (PCI) is widely used in treatment of acute coronary syndrome (ACS) clinically. It is believed that Danhong injection (DHI) extracted from salviae miltiorrhizae and flos carthami combined with PCI could increase the therapeutic efficacy on ACS. We provide an updated meta-analysis with detailed information on combination of DHI and PCI therapy.Materials and Methods: Electronic databases were searched for appropriate articles without language limitations on key words before October 22, 2017. All trails were screened according to certain criteria. Quality of eligible studies was also assessed. We made a detailed record of outcome measurements. RevMan 5.3 software was used to perform the meta-analysis.Results: 14 articles involving 1533 patients with ACS were selected. Compared to PCI treatment alone, total efficacy rate (TER) was enhanced and major adverse cardiovascular events (MACE) were reduced significantly for the combination of DHI and PCI (P < 0.00001). Vascular endothelial function was improved by significantly decreasing the contents of ET-1, vWF and increasing the levels of NO and FMD (P < 0.00001). The serum levels of IL-1, IL-6, IL-18, TNF-α, LpPLA2, MMP-9, and pentraxin-3 were significantly decreased (P < 0.00001), whereas IL-10 in serum was increased (P < 0.00001), indicating a stronger anti-inflammatory effect of the combination. The combination therapy decreased the serum levels of CD62P, PAGT, PADT, FIB-C significantly (P < 0.05), which was beneficial for preventing coagulation of platelets. Blood lipid was also affected by regulating TC, TG, LDL, and HDL, but the results were not statistically significant (P > 0.05). Cardiac function was improved by increasing LEVF (P = 0.006) but not LVED (P = 0.08). The combination treatment was associated with an improvement in antioxidant effect by decreasing MDA and increasing SOD significantly (P < 0.00001).Conclusion: Combination of DHI and PCI in treatment of ACS could improve TER and reduce incidence of MACE after PCI therapy. These effects may be mediated by combined actions of several mechanisms. However, these results of this study should be handled cautiously due to the limitations of this research. Several rigorous RCTs are in need to confirm these findings.