Latest ArticlesThe emerging nano-black phosphorus materials have created a new platform for biomedical research. Nano-black phosphorus has the following advantages: black phosphorus can produce singlet oxygen under near-infrared light irradiation, so it can be used as a photosensitizer for photodynamic therapy; black phosphorus has extensive light absorption in the long wavelength region, and this near-infrared photothermal property can be used in photothermal therapy. The high specific surface area and unique fold structure of the black phosphorus nanosheet make it have very high drug loading.This paper mainly reviews the applications of black phosphorus in biological imaging, photothermal therapy, photodynamic therapy, and as a drug carrier in recent years. Based on the photoelectric properties of black phosphorus nanomaterials combined with intelligent drug delivery platform, the synergistic effects of light/heat/chemistry, light/chemistry/gene, and light/chemistry/immunity can be produced, which has a broad application prospect.
In the treatment of hypertensive crisis, the novel Rho kinase inhibitor DL0805-2 can rapidly lower systematic blood pressure, reduce pulmonary artery pressure, and has a significant protective effect on lung injury.This experiment intends to evaluate the efficacy of DL0805-2 against pulmonary arterial hypertension (PAH) and preliminarily reveals its underlying mechanism. Animal welfare and experimental procedures are in accordance with the provision of the Animal Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences. Sprague Dawley (SD) rats were randomly divided into DL0805-2 low, medium, and high dose groups(1, 3, and 10 mg·kg-1), bosentan positive control group, model group, and blank control group. The drug was administered daily on the 7th day after model establishment by monocrotaline injection. On the 25th day of the experiment, relevant indicators were examined to observe the therapeutic effect of DL0805-2 on pulmonary hypertension. DL0805-2 significantly relieved the abnormal changes in the physiological parameters related to PAH induced by monocrotaline, including reducing right ventricular systolic pressure, alleviating cardiac damage caused by pressure overload, and reducing the levels of endothelin-1 and inflammatory factors in lung tissues.DL0805-2 also attenuated pulmonary arteries remodeling. It was preliminarily discovered that DL0805-2 exerts preventive and therapeutic effect on PAH through Rho-kinase pathway. Our results suggested that DL0805-2 had good therapeutic effects on monocrotaline-induced PAH rat model. It intervened early in the disease process, effectively prevented the development of the disease, and reduced the mortality of the diseased animals. The mechanism is related to Rho-kinase pathway.
The study is to investigate the effect of glaucocalyxin A(GLA) on mast cell-mediated anaphylaxis.The animal welfare and experimental process of this experiment followed the regulations of the Animal Ethics Committee of Yanbian University. BALB/c mice were used in the animal experiment and randomly divided into five groups, control group, model group, and GLA low, medium, and high dose groups(10, 20, and 40 mg·kg-1). Mice were sensitized by intradermal injection of anti-dinitrophenyl-immunoglobulin E(DNP-IgE) into the ears and challenged with a mixture of DNP-human serum albumin(HSA) and 4% evans blue into the tail veins to prepare an animal skin passive cutaneous anaphylaxis(PCA) model, which was collected from both ears for measurement of dye staining and histology. Rat peritoneal mast cells(RPMCs) were used in the cell experiment and divided into control, IgE + antigen(Ag), and IgE + Ag + GLA groups to determine histamine release as well as calcium influx levels. High-affinity IgE receptor(FcεRI)-mediated signaling pathway proteins and HMGB1/TLR4/NF-κB(high mobility group box 1/toll like receptor 4/nuclear transcription factor kappa B) signaling proteins were detected by Western blot. The results of animal experiments suggest that GLA inhibits PCA, reduces evans blue dye exudation, and reduces ear inflammation and ear thickness in mice. The results of cellular experiments suggested that GLA could reduce histamine release and calcium influx, and inhibit tumor necrosis factor-α(TNF-α), interleukin(IL)-4, IL-13, and IL-1β production; Western blot results showed that GLA inhibited FcεRI-mediated phosphorylation levels of spleen tyrosine kinase(Syk), Lck/Yes novel tyrosine kinase(Lyn), tyrosine kinase Fyn(Fyn), growthfactor receptor-bound protein 2(Gab2), and phospholipase C(PLC) γ1, while GLA inhibited HMGB1/TLR4 signaling pathway to limit NF-κB p65 nuclear metastasis. The results indicate that GLA inhibits mast cell degranulation and attenuates allergic inflammation through the HMGB1/TLR4/NF-κB signaling pathway.
As a Ginkgo biloba extract preparation, shuxuening injection has a unique advantage in the prevention and treatment of acute and subacute stroke, but its main active ingredient is still unclear. Using a subacute model of stroke in mice constructed earlier, we further explored the contribution and mechanism of the two main components of total ginkgo flavonol glycosides and total ginkgolides in facilitating the neurofunctional recovery in stroke-induced mice. The pharmacodynamics was mainly evaluated by neurobehavioral changes, cerebral infarction volume, blood-brain barrier permeability and brain edema. The pathway and targets were predicted by transcriptome and network pharmacology. Finally, the mechanism was verified at the mRNA and protein levels. The results showed that the beneficial effect of total ginkgolides was greater than that of total ginkgo flavonol glycosides in both the pharmacodynamics and the regulatory mechanism of granulocyte adhesion and diapedesis involving granulocyte colony-stimulating factor(G-CSF), macrophage-1 antigen(MAC-1) and E-selectin. These findings suggest that shuxuening injection may improve the prognosis for mice with subacute stroke by down-regulating GCSF-mediated granulocyte adhesion and diapedesis pathway mainly through the total ginkgolide components. This finding is expected to provide reference for optimizing prescription and searching for natural drugs for targeting the treatment of ischemic stroke prognosis. The animal experiments in this study followed the regulations of Animal Ethics Committee of Tianjin University of Traditional Chinese Medicine.
Natural deep eutectic solvent(NDES) is a kind of deep eutectic solvents(DESs) which is composed of natural substances with good biocompatibility. Those substances can function as hydrogen bond donor and acceptor, such as choline, amino acids, sugars, etc. NDES have been widely used in many fields due to their advantages of low cost, easy preparation and environmental friendliness. It is especially suitable for the pharmaceutical industry because of its good biocompatibility and safety for use. In this paper, we firstly review the molecular simulation methods for current design of DESs from the formation principle. And then, the materials and preparation of NDES are reviewed and the physicochemical properties are further described. Finally, we review the current application of NDES in pharmaceutics including increasing drug solubility, promoting drug permeability and enhancing oral drug absorption, and meanwhile their future applications in pharmaceutics were also prospected.
With the implementation of the two-child policy and the growing demand for child health, pediatric medication has been arousing widespread social concern. To develop the drugs suitable for children, including new compounds, new specifications and new dosage forms, is urgently required for pharmaceutical researchers. In this review, several technical bottlenecks for pediatric oral liquid preparations, as well as the novel strategies involved in drug nanocrystals, self-microemulsion, ion exchange resin and Pickering emulsion were discussed, which may be benefit to play a theoretical guiding role in the research and development of children's oral liquid formulation.
This study aims to investigate the effect of baicalein on the metastasis of esophageal squamous cell carcinoma(ESCC) cells, and to elucidate the potential molecular mechanisms. Wound healing and Transwell migration and invasion assays were performed to detect the effect of baicalein on the migration and invasion of EC9706 and KYSE30 cells; the nude mice models of lung metastasis were applied to examine the function of baicalein in metastasis of ESCC by using KYSE30 cells. All animals were received humane care according to the Institutional Animal Care Guidelines approved by the Experimental Animal Ethical Committee of Henan University. Western blot assay was used to detect the protein levels of ERK/ELK-1/Snail signaling pathway. The data showed that baicalein significantly inhibited the migration and invasion of EC9706 and KYSE30 cells; Mechanistically, baicalein treatment led to a dramatically reduced expression of phosphorylated extracellular signal-regulated kinase 1/2(p-ERK1/2, T202/Y204), p-ETS-domain containing protein-1(p-ELK-1, S383), Snail, N-cadherin, and Vimentin, and a statistical increase of E-cadherin expression in EC9706 and KYSE30 cells; Furthermore, the inhibition of ERK1/2 by U0126 or siRNA remarkably enhanced the effect of baicalein on the above proteins. In summary, baicalein probably inhibits the migration, invasion, and metastasis of ESCC cells via blocking the ERK/ELK-1/Snail signaling pathway.
With the in-depth study of related substances and the development of consistency evaluation of generic drugs, relative correction factors are gaining increasing attention. By analyzing the domestic and foreign literature on correction factors in recent years, this paper describes the correction factor component, the current measurement method and its application. The rules and key points of use of an impurity correction factor and its determination and application are described, and some problems in its determination and application are discussed, providing a reference and basis for the standardization of research on impurity correction factors in the future.
Long non-coding RNA (lncRNA) has a wide range of biological functions in epigenetic, cell cycle, cell differentiation and other life activities, and that affect the development and differentiation of immune cells and the maintenance of homeostasis in the immune system. CD4+ T cell subsets are heterogeneous cells with different functions, including promoting the proliferation and differentiation of T cells, B cells and other immune cells, and coordinating related functions between immune cells. Autoimmune disease (AID) is a chronic inflammatory disease caused by an autoantigen immune reaction. lncRNA and CD4+ T cell subsets are involved in the occurrence and progression of the disease. This article reviews the relationship between lncRNA and the differentiation of AID CD4+ T cell subsets.
Wound healing is a complex and highly regulated process to maintaining the skin barrier function. Wounds of diabetic patients are hard or even not healing. Non-healing diabetic foot ulcers can lead to lower-extremity amputations. Diabetic wound healing problem is the main complication that leads to high disability rate of diabetes and can threaten the lives in severe cases. The healing of skin wounds requires the synergy of multiple factors to restore the injured skin to its barrier function. The mechanisms that cause it difficult to heal diabetic wounds are complex, including oxidative stress, chronic inflammation, decreased neovascularization, peripheral neuropathy, and imbalance of extracellular matrix accumulation and remodeling. This review classifies mechanisms of diabetic wound healing and provides a reference for its further research.