Latest ArticlesThe 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.
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.
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.
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.
Dendrobium officinale Kimura et Migo (D. officinale) has been used as a valuable traditional Chinese medicine for more than 2 000 years in China. Modern research has confirmed a wide range of pharmacological activities, such as regulating blood sugar, improving gastrointestinal inflammation, and regulating immunity. Polysaccharides are the main active ingredients of D.officinale. With the intensive studies of the pharmacological activities of D.officinale, evidence for the pharmacological effects and potential mechanisms of D.officinale polysaccharides has increased dramatically. In this review, we summarized the latest progress in the pharmacological and mechanical studies of D.officinale polysaccharides, and based on the pharmacological efficacy and oral absorption and utilization characteristics of D.officinale polysaccharides, it is proposed that regulating the gut microbiota may be one of the key mechanisms for D.officinale to exert its beneficial effects. Research on the mechanism of D.officinale polysaccharides puts forward new research directions and prospects.
Dithiocarbamates and their derivatives with unique molecular structures possess diverse biological activities, which have become the research focus in the chemical and pharmaceutical fields in recent years. Here, we will review the structures, synthesis as well as biological activities of dithiocarbamates and their derivatives in anti-oxidation, anti-virus, anti-bacterial, anti-tumor and anti-Alzheimer's disease, and make a prospect for their development in the future.
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.
Drug-drug complexes play important roles in improving the physicochemical properties of drugs including the solubility, dissolution rate and stability of the active pharmaceutical ingredients (APIs). In this paper, the design, synthesis, characterization, changes in physicochemical and pharmacologic properties, structural polymorphisms and the research and development pipelines of a variety of drug-drug cocrystals/salts synthesized based on the crystal engineering design are reviewed. This may provide theoretical support for the development of the new solid-state combinational drugs.
The aim of this research is to investigate the effects of resveratrol on the inflammatory factors, oxidative stress indexes and the related genes of nuclear factor erythroid-2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway in RAW264.7 macrophages induced by monosodium urate (MSU) and to provide a theoretical basis for the treatment of acute gouty arthritis (AGA). Different concentrations of resveratrol were used to treat RAW264.7 cells for 5 hours, then MSU was added to stimulate them for 24 hours. The proliferation of RAW264.7 cells were detected by CCK-8 method. The level of tumor necrosis factor α secreted by cells were detected by ELISA method. The content of reaction oxygen species (ROS) in cells were detected by 2', 7'-dichlorodi-hydrofluorescein diacetate (DCFH-DA) probe method. The contents of superoxide dismutase (SOD) and malonaldehyde (MDA) in cells were detected by the kits. The expression of Nrf2, Kelch like ECH related protein 1 (Keap1), NAD(P)H quinone oxidoreductase 1 (NQO1), HO-1 mRNA were detected by real time PCR method. The results showed that resveratrol could inhibit the proliferation of RAW264.7 cells, significantly inhibit the TNF-α level of RAW264.7 cells induced by MSU, significantly inhibit the expression of ROS and MDA, and increase the expression of SOD in RAW264.7 cells induced by MSU. Resveratrol could reduce the expression of Keap1 mRNA in RAW264.7 cells induced by MSU, and increase the expression of Nrf2, NQO1, HO-1 mRNA. It is suggested that resveratrol can inhibit the inflammatory response of RAW264.7 macrophages induced by MSU, and improve the antioxidant capacity of macrophages by regulating Nrf2/HO-1 signal pathway.
To screen active components of Desmodium styracifolium in protecting calcium oxalate monohydrate (COM) -induced human proximaltubular epithelial cell (HK-2) damage model, and furtherly explore its mechanism of action, total flavonoids of Desmodium styracifolium (TFDS) and eight flavonoids (schaftoside, isoschaftoside, vicenin-2, isovitexin, isoorientin, apigenin, luteolin and genistein) were tested by COM-induced HK-2 damage model. MTT assay was used to detect the effects of different components on the cell viability of COM-induced HK-2 damage model. The lactate dehydrogenase (LDH) release in the cell supernatant and the activity level of superoxide dismutase (SOD) and reactive oxygen species (ROS) of cell were detected by the kit. Western blot was used to detect the expression levels of NLRP3, caspase-1, HMGB1 in HK-2 of different groups. Compared with the model group, the cell activity was significantly increased after 24 h co-culture with TFDS and four flavonoids (isoorientin, apigenin, genistein and luteolin). These active components can reduce the LDH leakage and ROS in cell supernatant and increase the activity of SOD, with regulating the expression of NLRP3, caspase-1, HMGB1. TFDS, apigenin, isoorientin, luteolin and genistein can protect COM-induced HK-2 cell damage, including enhancing cell viability, protecting cell membrane integrity and enhancing oxidative stress, and regulate the expression of proteins related to NLRP3 inflammasome.
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