We prepared moxifloxacin (MXF) loaded nanoparticles by nano-precipitation/self-assembly method, then compared the antibacterial activity of MXF and MXF loaded nanoparticles, and investigated the antibacterial mechanism of MXF loaded nanoparticles against Pseudomonas aeruginosa in vitro. The physicochemical properties such as particle size and zeta potential were investigated by laser particle size analyzer. The in vitro release characteristics were investigated by high performance liquid chromatography (HPLC). The effect of nanoparticles on HBE cells viability was investigated by CCK-8 assay. In addition, the in vitro antibacterial activity was investigated by minimum inhibitory concentration (MIC) assay, biofilm formation assays and transmission electron microscope (TEM) observation, then the antibacterial mechanism was initially explored. The particle size measurement showed that the nanoparticles had a size of 332.5 ±2.7 nm, a polymer dispersion index (PDI) of 0.125 ±0.053, a zeta potential of -24.3 ±1.7 mV, and a uniform particle size distribution, drug loading content was (6.02 ±1.27)%, encapsulation efficiency was (16.69 ±1.17)%. The TEM results show that the nanoparticles have a spheroidal structure, and the particle size and distribution are consistent with the particle size measurement results. The nanoparticles can be effectively and rapidly released in phosphate buffer saline (PBS), releasing about 70% in 24 h, and releasing 87% in 72 h, and almost completely releasing the MXF at 120 h. At the same time, compared with moxifloxacin free drug, its MIC value is 8 μg·mL^-1, which is 1/2 of MXF solution, and can significantly inhibit the formation of bacterial biofilms. It has well antibacterial activity in vitro and can be targeted to the surface of bacteria to exert its efficacy and improve the antibacterial effect. The moxifloxacin nanoparticles prepared in this study has a uniform particle size distribution, well drug release performance and antibacterial effect, and provides new ideas and strategies for the treatment of bacterial lung infection and the development of new antibacterial nanoformulations.

We investigated the ability of 3-bromopyruvic acid to increase the sensitivity of tamoxifen-resistant MCF-7/TR cells to tamoxifen and to explore the underlying mechanism. 4-Hydroxy tamoxifen (4-OHT) is the active form of tamoxifen in vivo and was used in this study. The effect of 3-bromopyruvic acid on the viability of MCF-7/TR cells was measured by MTT assay and the morphology of MCF-7/TR cells was observed with an inverted microscope. The results show that 3-bromopyruvic acid at 40 μmol·L^-1 has no significant effect on the viability of MCF-7/TR cells, and this concentration was used in the subsequent experiments:3-bromopyruvic acid significantly increased the inhibitory effect of 4-OHT on the viability of MCF-7/TR cells, with a reversal-fold of 1.91, as determined by MTT assay; the lactate level, determined with a lactate detection kit, and the expression levels of GLUT1, HK2, and LDHA in MCF-7/TR cells as measured by immunoblotting were significantly higher than in MCF-7 cells; and compared with 4-OHT treatment alone, the combination treatment of 3-bromopyruvic acid and 4-OHT significantly reduced the lactate level and the expression of GLUT1, HK2, LDHA in MCF-7/TR cells. The above results show that 3-bromopyruvic acid increases the sensitivity of MCF-7/TR cells to tamoxifen, and the mechanism is related to the inhibition of aerobic glycolysis.

The technology of lipid-drug conjugates is developed on the basis of prodrug principle, which overcomes some drawbacks of drugs via increasing the lipophilicity of hydrophilic or poorly soluble drugs to promote the absorption of drugs and enhance the curative effect. This article sums up the research progress of lipid-drug conjugates from the chemical synthesis methods of conjugates, the types of conjugates, the influence on biological activity of drugs, the application in nanoparticles for drug delivery and the mechanism of absorption and degradation.

Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disease, which is mainly characterized by hyperandrogenemia, rare or anovulation, and polycystic ovarian changes. PCOS is seriously harmful and its causes are complex, which has not yet been clarified. Studies have shown that non-coding RNAs play important roles in the development of PCOS, including the regulation of hormone metabolism and follicle development. Exosomes are natural nano-scale membrane vesicles that contain cell-specific proteins, lipids, nucleic acids, and other biologically active molecules. Exosomes are important mediators for intercellular communication and new targets for disease diagnosis and treatment. Recent studies have shown that as an important component of follicle microenvironment, exosome is closely related to the pathogenesis of PCOS. Exosome and exosomal non-coding RNAs are expected to serve as potential new diagnostic and therapeutic targets for PCOS. In this review, we will summarize the function of exosome and exosomal non-coding RNA in the pathogenesis, diagnosis, and treatment of PCOS.

The tumor contains abundant new vessels, which are unevenly distributed, irregular, and branch-disordered. Angiopoietin (Ang) and tyrosine kinase receptor Tie mediate stable maturation of angiogenesis. Ang1 mainly plays a role in promoting vascular stabilization, and Ang2 is highly expressed in vessels, which makes the structure and function of vessels abnormal. Leaked vessels provide opportunities for invasion and metastasis of circulating tumor cells. Targeting the Ang/Tie axis to correct the abnormal state of vessels and promote its normalization, combined with chemotherapy drugs or immunotherapy, play a synergistic effect against tumors. This article summarizes the role of Ang/Tie axis in tumor angiogenesis and metastasis, and it aims to provide new ideas and strategies for clinical treatment of tumors.

Ischemic stroke is one of the leading causes of death and disability worldwide. A large number of preclinical studies have demonstrated that exogenous cell-based therapies such as mesenchymal stem cell transplantation can promote brain function recovery in the subacute phase of stroke. Emerging data indicate that mesenchymal stem cell-derived exosomes play a key role in mediating tissue repair by participating in intercellular signal transduction and transferring biological information especially microRNA to recipient cells, which affects endo-genous recovery in ischemic brain tissue after injury. In this review we briefly describe the characteristics and biological functions of exosomes and exosomal microRNA, and discuss the therapeutic effects of mesenchymal stem cell-derived exosomes on ischemic stroke from different perspectives. Finally, we outline the potential clinical value of exosomes and challenges of translating these therapies into clinical trials.

In recent years, the number of clinical trials of stem cell products has increased, and the research and development technology and evaluation system have developed rapidly. Human pluripotent stem cell (hPSC)-derived cellular products are in the phase Ⅰ/Ⅱ stage of clinical trials. Related products include hPSC-derived neurons, retinal pigment epithelial cells, pancreatic beta cells, etc. They are generally used for the repair and replacement of functional cells related to degenerative diseases and genetic diseases via local transplantation. So far, no similar products have been officially approved on market. As hPSC possesses multi-directional differentiation potential and the ability to form teratoma in vivo, compared with other stem cell products, hPSC-derived cellular products have relatively higher risk of tumorigenicity, longer differentiation induction cycle, more complex production process, together with the rapidly updating quality characterization methods, which pose challenges to the scientific evaluation of their human applications. Based on the problems in the recent review and communication of clinical trial applications of stem cell products, and with reference to the relevant technical guidelines, this paper proposes the chemistry, manufacturing, and controls review considerations on the manufacturing process and quality study of hPSC-derived cellular products. We hope to improve the communications between developers and regulators.

Malignant tumor is a disease that severely threaten human health. Common chemotherapeutical drugs currently used in clinical practice have some problems in severe side effects and chemoresistance. In contrast, natural venom peptides and artificially designed targeting peptides have excellent biological activities and potential druggability due to their small molecular weights and high affinity to tumor tissues. Thus, the methods for the discovery of anti-tumor peptides have attracted much attention. In this paper, we summarized the types of anti-tumor peptides from recent literatures. Then, we systematically reviewed screening theories, methods and applications based on traditional chromatographic separation, peptidomics, phage display, phenotypic screening, and artificial intelligence. These strategies and technologies will provide a methodological reference for accelerating anti-tumor peptides research.

Human pathogenic coronaviruses can be divided into seven types, namely HCoV-229E, HCoV-OC43, HCoV-HKU1, HCoV-NL63, SARS-CoV, MERS-CoV and SARS-CoV-2. Among them, Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS) and Corona Virus Disease 2019 (COVID-19), which are caused by the last three coronaviruses respectively, are enormous threats that challenge human health and social and economic development. Despite the huge investment in drug development for pathogenic coronaviruses, there is no specifically effective anti-coronavirus drug approved so far. In this review we systematically summarize 146 representative anti-coronavirus active compounds reported in the past 20 years and list 26 potential target proteins involved in the process of viral infection and replication. In addition, we predict the target proteins of those active compounds with unclear antiviral activity mechanisms. We hope that the information will be useful to accelerate the development of new anti-coronavirus drugs.

The intestinal flora is a diverse microbial community living in the digestive tract of humans and animals. This microbial community can modify drugs in unpredictable ways, leading to changes in the pharmacokinetics of drugs in vivo and affecting their clinical efficacy. Here we review drug metabolism mediated by intestinal flora from three aspects:prodrug activation, drug inactivation, and toxicity. The effect of the stable hypoxic environment on the composition and quantity of intestinal flora and the effect on drug metabolism are discussed. Understanding the influence of intestinal flora on drug metabolism is not only conducive to individualized medication, but also conducive to rational drug design, allowing us to predict and understand individual drug response and regulate the intestinal microbiome to improve drug efficacy, thus promoting personalized medicine.