Advances in oxidative stress in pathogenesis of diabetic kidney disease and efficacy of TCM intervention.

Diabetic kidney disease (DKD) is a common complication of diabetes and has become the leading cause of end-stage kidney disease. The pathogenesis of DKD is complicated, and oxidative stress is considered as a core of DKD onset. High glucose can lead to increased production of reactive oxygen species (ROS) via the polyol, PKC, AGE/RAGE and hexosamine pathways, resulting in enhanced oxidative stress response. In this way, pathways such as PI3K/Akt, TGF-ß1/p38-MAPK and NF-κB are activated, inducing endothelial cell apoptosis, inflammation, autophagy and fibrosis that cause histologic and functional abnormalities of the kidney and finally result in kidney injury. Presently, the treatment for DKD remains an unresolved issue. Traditional Chinese medicine (TCM) has unique advantages for DKD prevention and treatment attributed to its multi-target, multi-component, and multi-pathway characteristics. Numerous studies have proved that Chinese herbs (e.g., Golden Thread, Kudzuvine Root, Tripterygium glycosides, and Ginseng) and patent medicines (e.g., Shenshuaining Tablet, Compound Rhizoma Coptidis Capsule, and Zishen Tongluo Granule) are effective for DKD treatment. The present review described the role of oxidative stress in DKD pathogenesis and the effect of TCM intervention for DKD prevention and treatment, in an attempt to provide evidence for clinical practice.

Active edible films with plant extracts: a updated review of their types, preparations, reinforcing properties, and applications in muscle foods packaging and preservation.

Currently, edible films have been increasingly explored to solve muscle food spoilage during storage, especially through the incorporation of plant extracts to develop edible packaging materials. Natural polymers matrices with plant extracts are befitting for fabricating edible films by casting methods. In the films system, the structure and physicochemical properties were strengthened via chemical interactions between active molecules in plant extracts and the reactive groups in the polymer chain. The antibacterial and antioxidant properties were dramatically reinforced through both physical and chemical actions of the plant extracts. Additionally, edible films imbedded with color-rich plant extracts could be considered as potential sensitive indicators to monitor the spoilage degree of muscle foods in response to change in gas or temperature. Furthermore, these films could increase sensory acceptability, improve quality and prolong the shelf life of muscle foods. In this article, the types, preparation methods and reinforcing properties of the edible films with plant extracts were discussed. Also, the applications of these films were summarized on quality maintenance and shelf-life extension and intelligent monitoring in muscle foods. Finally, a novel technology for film preparation achieving high-stability and sustained release of active compounds will become an underlying trend for application in muscle food packaging.

Progress and Prospects of Research Ideas and Methods in the Network Pharmacology of Traditional Chinese Medicine.

In recent years, the emerging network pharmacology has been extensively applied to the field of traditional Chinese medicine and has made great contributions to the modernization of TCM. Therefore, this paper provides an overview of the progress of research ideas and methods in the network pharmacology in the last few years in the field of traditional Chinese medicine and presents insights into future research methods and ideas in the network pharmacology. Problems with the current network pharmacology are discussed and prospects of its future development are put forward.

Activation of ATM/Chk2 by Zanthoxylum armatum DC extract induces DNA damage and G1/S phase arrest in BRL 3A cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Zanthoxylum armatum DC is a traditional medicinal plant. It is widely used in clinical treatment and disease prevention in China, India and other regions. Modern studies have reported the phytotoxicity, cytotoxicity and the animal toxicity of Zanthoxylum armatum DC, and the damage of genetic material has been observed in plants, but the detailed mechanism has not been explored. Besides, the toxicity of normal mammalian cells has not been evaluated. AIM OF THE STUDY: To evaluate the effects and underlying mechanism of genetic material damage in BRL 3A cells induced by Zanthoxylum armatum DC. MATERIALS AND METHODS: Ultra-High Performance Liquid Chromatography and Orbitrap High-Resolution Mass Spectrometry was used for identification of compounds in methanol extract of Zanthoxylum armatum DC. BRL 3A cells were incubated with different concentrations of methanol extract of Zanthoxylum armatum DC (24 h). The cytotoxicity of extract was assessed with cell viability, LDH release rate, and ROS production. The damage of genetic material was assessed with OTM value of comet cells, cell cycle and the expression levels of p-ATM, p- Chk2, Cdc25A, and CDK2. RESULTS: Ultra-High Performance Liquid Chromatography and Orbitrap High-Resolution Mass Spectrometry investigation revealed the presence of compounds belonging to flavonoid, fatty acid and alkaloid groups. The viability of BRL 3A cells was reduced in a time-dose dependent manner treated by methanol extract of Zanthoxylum armatum DC. It increased LDH release rate and ROS production, activated the DNA double strand damage marker of γH2AX and produced comet cells. In addition, methanol extract of Zanthoxylum armatum DC caused ATM-mediated DNA damage, further phosphorylated Chk2, inhibited cell cycle related proteins, and arrested the G1/S cycle. CONCLUSIONS: Methanol extract of Zanthoxylum armatum DC induces DNA damage and further leads G1/S cell cycle arrest by triggering oxidative stress in the BRL 3A cells. This study provides some useful evidences for its development as an antitumor drug via activation of ATM/Chk2.

Identification of Oxidative Stress-Related Biomarkers in Diabetic Kidney Disease.

Background: Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease throughout the world. In kidney disease, oxidative stress has been linked to both antioxidant depletions and increased reactive oxygen species (ROS) production. Thus, the objective of this study was to identify biomarkers related to oxidative stress in DKD. Methods: The gene expression profile of the DKD was extracted from the Gene Expression Omnibus (GEO) database. The identification of the differentially expressed genes (DEGs) was performed using the "limma" R package, and weighted gene coexpression network analysis (WGCNA) was used to find the gene modules that were most related to DKD. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed using "Org.Hs.eg.db" R package. The protein-protein interaction (PPI) network was constructed using the STRING database. The hub genes were identified by the Molecular Complex Detection (MCODE) plug-in of Cytoscape software. The diagnostic capacity of hub genes was verified using the receiver operating characteristic (ROC) curve. Correlations between diagnostic genes were analyzed using the "corrplot" package. In addition, the miRNA gene transcription factor (TF) network was used to explain the regulatory mechanism of hub genes in DKD. Results: DEGs analysis and WGCNA-identified 160 key genes were identified in DKD patients. Among them, nine oxidative stress-related genes were identified as candidate hub genes for DKD. Using the PPI network, five hub genes, NR4A2, DUSP1, FOS, JUN, and PTGS2, were subsequently identified. All the hub genes were downregulated in DKD and had a high diagnostic value of DKD. The regulatory mechanism of hub genes was analyzed from the miRNA gene-TF network. Conclusion: Our study identified NR4A2, DUSP1, FOS, JUN, and PTGS2 as hub genes of DKD. These genes may serve as potential therapeutic targets for DKD patients.

Novel biomimetic dual-mode nanodroplets as ultrasound contrast agents with potential ability of precise detection and photothermal ablation of tumors.

PURPOSE: Molecule-targeted ultrasound imaging has attracted extensive attention for precise diagnosis and targeted therapy of tumors. The aim of this research is to prepare novel biomimetic dual-mode nanoscale ultrasound contrast agents (UCAs), which can not only evade the immune clearance of reticuloendothelial system, but also have the potential ability of precise detection and photothermal ablation of tumors. METHODS: In this study, for the first time, the novel biomimetic UCAs were prepared by encapsulating liquid perfluorohexanes with red blood cell membranes carrying IR-780 iodide and named IR780-RBCM@NDs. The characteristics of that were verified through the particle size analyzer, scanning electron microscopy, transmission electron microscopy and laser scanning confocal microscopy. The stability of IR780-RBCM@NDs at 37 °C was explored. The abilities of immune escape, dual-mode imaging and photothermal effect for IR780-RBCM@NDs were verified via in vitro experiments. RESULTS: The novel prepared nanodroplets have good characteristics such as mean diameter, zeta potential, and relatively stability. Importantly, the integrin-associated protein expressed on the surface of RBCMs was detected on IR780-RBCM@NDs. Then, compared with control groups, IR780-RBCM@NDs performed excellent immune escape function away from macrophages in vitro. Furthermore, the IR-780 iodide was observed on the new nanodroplets and that was able to perform the dual-mode imaging with near-infrared fluorescence imaging and contrast-enhanced ultrasound imaging after the phase change. Finally, the effective photothermal ablation ability of IR780-RBCM@NDs was verified in tumor cells. CONCLUSION: The newly prepared biomimetic IR780-RBCM@NDs provided novel ideas for evading immune clearance, performing precise diagnosis and photothermal ablation of tumor cells.

Efficacy and safety of Zuojin Pill for chronic gastritis: Protocol for a systematic review of randomized controlled trials.

BACKGROUND: Chronic gastritis (CG), as the highest incidence of gastrointestinal diseases, has been gradually increasing around globally. With the obvious disadvantages of standard treatment, more and more people ask the traditional Chinese medicine for help in the treatment of CG. As a traditional Chinese medicine compound, Zuojin Pill (ZJP) has a long history of clinical application in the treatment of digestive system diseases. Whereas, neither systematic nor meta-analysis of randomized controlled trials explain the efficacy and safety of ZJP in treating CG. Thus, we provide a protocol to evaluate the efficacy and safety of ZJP for CG. METHODS: From the beginning to December 2019, the following electronic databases will be searched for studies in English or Chinese: the Cochrane Library, Embase, PubMed, Web of Science, the Chinese National Knowledge Infrastructure, the Chinese Biomedical Literature Database, the Chinese Scientific Journal Database, and the Wanfang Database. Clinical efficiency, helicobacter pylori infection clearance rate, quality of life and symptom scores will be measured as primary outcomes. Meta-analysis will be performed using the Stata 15. OUTCOMES: This study will provide the current evidence of CG treated with ZJP from the several aspects including clinical efficiency, helicobacter pylori infection clearance rate, quality of life, symptom scores, the 1-year recurrent rate, efficacy under endoscopy and number of reported adverse events associated with the use of ZJP. CONCLUSION: The outcomes of this review will be served as a proof to evaluate if ZJP is effective in the treatment of CG. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42020155036.