ABSTRACT
Pneumoconiosis is the most common occupational disease in China, which severely endangers people's health. Depending on the inhaled air pollutants, pneumoconiosis is classified as anthracosis, silicosis, asbestosis, etc., among which silicosis is the most common and serious. Silicosis is a systemic, poor prognostic disease characterized by diffuse fibrosis of lung tissue, which is caused by long-term exposure to dust with high levels of free silicon dioxide (SiO2) in the occupational environment. Appropriate treatment in time is important for the disease. Unfortunately, no effective drugs have been approved to delay or even reverse pulmonary fibrosis caused by SiO2. This review briefly classifies potent therapeutic drugs and compounds in term of mechanisms, providing the probability for clinical treatment of silicosis.
ABSTRACT
Along with the progress of pharmaceutical science in the past century, the theme of pharmacology has gone through pseudo agent scheme, to ligand-receptor model, and then to the theory of targeted therapy today. Due to the success of drug R&D, current drug research keeps its focus mainly on drugs with single target and precise treatment, in which the molecular mechanism is relatively clear but the therapeutic efficacy is often limited. Thus, there is a big space for exploration in the field of pharmacology. In the past 30 years, several novel chemical drugs, originated from traditional Chinese medicine, have been identified and then used in clinic, provoking a strong interest to explore new theory for pharmacology, of which the term of "Biao Ben Jian Zhi" (treating diseases by directing symptoms and root causes) has demonstrated a promising nature. We consider this concept useful for future drug discovery, drug design and clinical therapy. In this review, example drugs such as berberine, metformin and azvudine, are discussed, and "drug Cloud" (dCloud) model is introduced to elaborate the mechanism of treating diseases by directing symptoms and root causes of diseases.
ABSTRACT
Gut microbiota is a complex and dynamic system, and is essential for the health of the body. As the "second genome" of the body, it can establish communication with the important organs by regulating intestinal nerves, gastrointestinal hormones, intestinal barrier, immunity and metabolism, thus affecting host′s physiological functions. Short chain fatty acid (SCFA), known as one important metabolite of intestinal microbiota, is regarded as a significant messenger of the gut-organ communication, due to its extensive regulation in the body′s immunity, metabolism, endocrine and signal transduction. In this review, we summarize the interaction between gut-liver/brain/kidney/lung axis and diseases, and focus on the role and mechanism of SCFA in the gut-organ communication, hoping to provide new ideas for the treatment of the related diseases.
ABSTRACT
The aim of this study was to investigate the efficacy and mechanism of Dengzhan Shengmai (DZSM) against nonalcoholic fatty liver diseases (NAFLD). The animal experiment program was reviewed and approved by the Ethics Committee of Institute of Materia Medica, Chinese Academy of Medical Sciences. The NAFLD model of Syrian golden hamsters was established by high fat diets. After 6 weeks of DZSM treatment, the serum lipid, hepatic lipid accumulation, liver function and inflammatory response were determined. The regulations of gut microbiota and short-chain fatty acids were detected by 16S rRNA gene sequencing and gas chromatography-mass spectrometry method, respectively. The gut barrier function was evaluated by enzyme linked immunosorbent assay (ELISA), reverse transcription-quantitative polymerase chain reaction (RT-qPCR), Western blot and histopathological methods and further verified in HepG2 cells. The results showed that the efficacy of DZSM against NAFLD was remarkably reduced after removal of the gut microbiota. The study of mechanism showed that DZSM significantly regulated the composition of gut microbiota, promoted the production and absorption of intestinal short-chain fatty acids, then leading to the reduction of hepatic lipid accumulation. Moreover, after DZSM treatment, the decreased lipopolysaccharide (LPS) level by improving the intestinal barrier function significantly inhibited the hepatic inflammation through down-regulating Toll like receptor 4 (TLR4)-nuclear factor kappa B (NFKB) signaling pathway. These results indicate that DZSM inhibits NAFLD via regulating intestinal microenvironment.
ABSTRACT
In recent years, with the improvement in living standards, the morbidity and mortality of cardiovascular and cerebrovascular diseases has increased markedly. Atherosclerosis is the main pathological basis for cardiovascular and cerebrovascular diseases, and there are many risk factors for atherosclerosis. The pharmacological effects of puerarin are broad, and considerable clinical data confirms that puerarin has a definite effect on cardiovascular diseases resulting from atherosclerosis. The use of puerarin for atherosclerosis has increased in recent years. This article reviews the effect and mechanism of puerarin on atherosclerosis.
ABSTRACT
In this study, the regulatory effects of chlorogenic acid (CGA) on the expression of programmed cell death ligand 1 (PD-L1) in esophageal squamous cell carcinoma (ESCC), as well as the role of interferon γ (IFN-γ), has been discussed using both in vitro and in vivo animal models. ESCC murine model was established according to the standard operating procedures (SOP) of Animal Experiment Center of Institute of Materia Medica, Chinese Academy of Medical Sciences. The expression of PD-L1 in esophageal tissues of murine models was analyzed using the microarray assay. Then, the results were verified by qRT-PCR, Western blot and immunohistochemistry (IHC) staining, the molecular mechanism was explored in KYSE180 and KYSE510 ESCC cells in vitro. The results showed that CGA could suppress the expression of PD-L1 in tumor tissues in murine models significantly, rather than the expression in KYSE180 and KYSE510 ESCC cells in vitro. However, after the pretreatment of IFN-γ, the expression of PD-L1 was significantly increased, then it was down-regulated by CGA in both dose- and time-dependent manner. Meanwhile, the expression of interferon regulatory factor 1 (IRF1), an upstream regulatory factor of PD-L1, was suppressed by CGA in both KYSE180 and KYSE510 pretreated with IFN-γ, which was consistent with the expression of PD-L1. These results indicate that CGA down-regulates the expression of PD-L1 in ESCC via IFN-γ-IRF1 signaling pathway, providing the molecular theoretical basis for exploration of new treatment of ESCC.
ABSTRACT
L-Proline-m-bis (2-chloroethyl) amino-L-phenylalanyl-L-norvaline ethyl ester hydrochloride (MF13) is a new anticancer tripeptide. Our previous study in vitro and in vivo showed that MF13 had anti-proliferative activities in a panel of human hepatocellular carcinoma (HCC) cell lines from different origin. In the present study, we focused on the inhibition effect on HCC of MF13 combined with other anti-cancer drugs. The results of combination chemotherapy in vitro indicated that the combination of MF13 with mitomycin C (MMC) at appropriate concentrations led to a synergistic effect; however, the combination of MF13 with vincristine (VCR) showed no synergistic effect. In the Bel-7402 tumor bearing nude mice, the antitumor effect of the groups of 2 mg·kg-1 MF13 + 2 mg·kg-1 MMC or 2 mg·kg-1 MF13 + 50 mg·kg-1 cyclophosphamide (CTX) exhibited synergistic anticancer efficacies while the group of 2 mg·kg-1 MF13 + 0.3 mg·kg-1 VCR did not have the same effect. Based on our data, we believe that MF13 can be considered as a potential agent against human hepatocellular carcinoma no matter how treated, alone or combined with other drugs.
ABSTRACT
CCR5, a membrane protein on cell surface, is a member of the G protein-coupled receptor superfamily and one of the major co-receptors for HIV-1 infection. The roles of CCR5 in HIV-1 infection have been elucidated since 1996. Because of the biological nature of CCR5, it has became a molecular target for the novel drugs against HIV-1. Antagonists for CCR5 could be grouped as following, chemokine derivatives, small molecule non-peptide compounds, monoclonal antibodies and peptides. The latest progress in this field is reviewed in this article.