Latest ArticlesChronic kidney disease(CKD) is a serious chronic disease with high incidence, poor prognosis, and a variety of complications. Indoxyl-sulfate(IS) and p-cresol sulfate(PCS) are two typical gut-derived uremic toxins, which are produced by the co-metabolism of intestinal microbes and the host. With the progression of CKD, gutderived uremic toxins such as IS and PCS accumulate in patients with CKD and thereafter accelerate the progression of CKD. Gut microbiota is closely related with CKD, and targeting gut microbiota to regulate gut-derived uremic toxins synthesis and metabolic pathways may be a promising strategy to delay the progression of CKD. In this paper, the relationship between gut microbiota, gut-derived uremic toxins, and CKD was analyzed, and the strategy to delay the progression of CKD by targeting gut microbiota and uremic toxins metabolism pathway was proposed.
The function of circulatory system, nervous system and endocrine system is significantly changed in hypoxic environments. These changes affect the absorption, distribution, metabolism, and excretion of drugs in the body. Drug metabolizing enzymes and transporters are the main factors affecting drug metabolism; microRNA(miRNA) can act directly on drug metabolizing enzymes and transporters and can regulate their genes through hypoxia-inducible factor, inflammatory cytokines, and nuclear receptors. This article reviews the effect of hypoxia on drug metabolizing enzymes and transporters and the mechanisms by which miRNA modulates these proteins and their expression during hypoxia.
Hyperlipidemia is a common disease with abnormal blood lipids and is an important risk factor for various cardiovascular diseases. Traditional Chinese medicine has the advantages of dependable lipid-lowering effects with few side effects and is widely used in the prevention and treatment of hyperlipidemia in China. However, due to the complex composition of traditional Chinese medicine and the many targets for treating hyperlipidemia, the mechanisms by which these medicines lower lipid levels are not well resolved. Lipidomics is a discipline that studies lipids and the interaction of lipids in biological systems. Lipidomics can identify and quantify the lipids in vivo under physiological and pathological conditions, helping to discover the potential biomarkers related to the lipid-lowering effects of traditional Chinese medicine and providing a basis for systematically studying the lipidlowering effect of traditional Chinese medicine. This review introduces the principal research methods used in lipidomics and summarizes the results and prospects of application of lipidomics in the research on the lipid-lowering effects of traditional Chinese medicine.
Chronic obstructive pulmonary disease and asthma are complex inflammatory diseases with airway obstruction as the main characteristics, and have become common respiratory diseases that seriously affect human health. Compared with the clinical use of PDE3 or PDE4 inhibitors alone, dual PDE3/4 inhibitors have synergistic anti-inflammatory and bronchodilator effects, and have attracted widespread attention in recent years. This article reviews the representative research results of dual PDE3/4 inhibitors currently in the preclinical and clinical research stages, summarizing their latest progress and their potential for the treatment of chronic obstructive pulmonary disease and asthma.
Cardiovascular disease is a principal cause of morbidity and death in the world. Although drug therapy has made great progress in the past few decades, there are still many deficiencies in the prevention and treatment of cardiovascular disease. Dyslipidemia is still a common risk feature and is not sufficiently controlled. A growing body of evidence suggests that the occurrence and development of cardiovascular disease is associated with many associated risk factors, such as higher low-density lipoprotein levels, lower high-density lipoprotein levels and high triglyceride levels. A number of clinical trials in patients with dyslipidemia have shown that actively decreasing low density lipoprotein cholesterol can significantly decrease cardiovascular events. ATP citrate lyase(ACLY) is a cytoplasmic homo-tetrameric enzyme. In the presence of adenosine triphosphate(ATP), ACLY catalyzes the conversion of citric acid and coenzyme A to acetyl-CoA and oxalyl acetate. ACLY is the main enzyme for the production of cytoplasmic acetyl-CoA, and cytoplasmic acetyl-CoA is the precursor required for de novo synthesis of cholesterol and fatty acids. Therefore, it is possible to reduce the production of acetyl-CoA and reduce the levels of cholesterol and triglycerides by inhibiting ACLY. ACLY can be used as a molecular target for reducing blood lipids, and there are an increasing number of studies on ACLY inhibitors. In this paper, the structure and mechanism of ACLY and its relationship with lipid metabolism are briefly introduced, and we review some current ACLY inhibitors.
The incidence of malignant melanoma, a highly fatal skin tumor, is on the rise worldwide. Melanomas are highly aggressive and have strong metastatic capability that leads to lethality. Recurrence occurs in patients with distant metastases, even with the latest treatments, and median survival is only a few months. At present, the prevention and treatment of melanoma includes surgical resection, chemotherapy, immunotherapy and targeted therapy. However, these strategies can lead to drug resistance and adverse effects. In recent years, an increasing number of studies have found that natural products have effective anti-melanoma activities, including inhibition of tumor growth, induction of cell apoptosis, inhibition of angiogenesis and metastasis and toxicity to tumor stem cells.In addition, several studies have reported that the combination of natural products and traditional anti-melanoma drugs can enhance the therapeutic efficacy. In this review we summarize the prevention and treatment of melanoma with natural products.
The determination and characterization of solid drug form polymorphisms plays an important role in drug quality control, selection of the production process and clinical efficacy evaluation. Vibrational spectroscopy is a powerful method for the characterization of drug polymorphisms. In this paper we review recent research and application advances in the polymorphic characterization of active pharmaceutical ingredients(APIs) and drug cocrystals/salts by using Fourier transform infrared(FTIR) and Raman spectroscopy to elucidate the characteristics of APIs and drug complexes. This may provide theoretical support for structural analysis during the development process for drugs.
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.
Nanomedicine has great potential in cancer therapy, but the complex tumor microenvironment greatly prevents nanomedicine from being effectively delivered into tumor in vivo. It has been widely accepted that the encapsulated drugs in the nanoparticles have to go through five major cascading steps, including blood circulation, accumulation in tumor, penetration into the depth of tumor tissue, internalization by tumor cells and then intracellular drug release, before they can exert the anti-tumor efficacy. Among the five steps, drug accumulation in tumor and penetration in the depth of tumor have been the two major issues undermines the antitumor efficacy of nanomedicine. This paper summarizes the new major progress in improving the tumor accumulation and penetration of nanomedicine, especially the technologies that appeared or developed in the last five years.
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.
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