Medicinal materials in China differ in quality by different ecological types. Our research group found that there were two ecotypes of domestic Panax quinquefolium L. according to the characteristics of ginsenosides, inside versus outside Shanhaiguan. The genetic and ecological mechanisms of quality variation of Panax quinquefolium L. is unknown. Based on the genetic-chemical-ecological strategy, transcriptome and HPLC technology were used for comprehensive correlation analyses of transcriptomic data, ginsenoside content and environmental climate ecological factors. The transcriptomic results showed that key genes of ginsenoside biosynthesis, such as HMGR, AS and FPS, were significantly down-regulated in the inside Shanhaiguan ecotype. HPLC results showed that the quality of outside Shanhaiguan ecotype Panax quinquefolium L. was higher than that of the inside ecotype, with the content of ginsenosides in outside Panax quinquefolium L. was higher than that of inside ecotype except Rb₂. Correlation analyses revealed that content of Panax quinquefolium L. ginsenoside is positively related to the expression levels of ginsenoside biosynthesis key genes (MK, HMGS, HMGR, and AS), and negatively related to the expression of glycosyl transferase (GT). The content of ginsenosides is negative related with climate factors, such as temperature, sunshine, and is positively related with moisture in both ecological environments. This study has provided a new mechanistic insight into the quality variations of two ecotypes for Panax quinquefolium L. and established a scientific basis for studying the ecological factors for the quality of traditional Chinese medicine.

A quantitative analytical method for multi-components with a single-marker (QAMS) was established for simultaneous determination of neochlorogenic acid, chlorogenic acid, caffeic acid, cryptochlorogenic acid, 1, 3-dicaffeoylquinic acid, 3, 4-dicaffeoylquinic acid, 3, 5-dicaffeoylquinic acid and 4, 5-dicaffeoylquinic acid in Artemisia capillaris Thunb standard decoction. The separation was performed on a Waters CORTECS T3 column (2.1 mm×100 mm, 2.7 μm), with the mobile phase consisting of 0.05% phosphate acid solution-acetonitrile for gradient elution. The column temperature was 30℃, and flow rate was 0.5 mL·min^-1. Using chlorogenic acid as an internal reference, the relative correlation factors of neochlorogenic acid, caffeic acid, cryptochlorogenic acid, 1, 3-dicaffeoylquinic acid, 3, 4-dicaffeoylquinic acid, 3, 5-dicaffeoylquinic acid and 4, 5-dicaffeoylquinic acid were calculated following UHPLC, as 0.928 0, 0.546 2, 1.099 8, 0.872 1, 1.086 8, 0.739 2, 1.056 6, respectively. The results were compared with those obtained by the external standard method to verify the feasibility, rationality and repeatability of QAMS method. There was no significant difference in assay results between QAMS and the external standard method. In conclusion, the QAMS method is accurate and feasible, and could be used to determine the content such as neochlorogenic acid, caffeic acid, cryptochlorogenic acid, 1, 3-dicaffeoylquinic acid, 3, 4-dicaffeoylquinic acid, 3, 5-dicaffeoylquinic acid and 4, 5-dicaffeoylquinic acid in Artemisia capillaris Thunb standard decoction.

Tenofovir disoproxil fumarate (TDF) is a nucleoside analogue that has been widely used for clinical treatment of human immunodeficiency virus (HIV) and hepatitis B virus (HBV) infection. The aim of this study was to investigate whether TDF has anti-Zika virus (ZIKV) activity in vitro. The inhibitory effect of TDF on ZIKV was detected by plaque reduction assay. Then, the anti-ZIKV activity of TDF at RNA level and protein level was verified by real time quantitative PCR and Western blot. Finally, MTT assay was used to determine the cytotoxicity of TDF. Our results showed that TDF not only reduced the formation of plaque after ZIKV infection, but also inhibited the replication of ZIKV RNA or expression of ZIKV NS2B protein. The 50% effective concentration (EC₅₀) of TDF in inhibition of ZIKV replication were 14.96-27.47 μmol·L^-1, while that of ribavirin was 56.01 ±12.16 μmol·L^-1, which served as the positive control. The cytotoxicity of TDF and ribavirin in Vero cells were very low, with their 50% cytotoxic concentration (CC₅₀) values being greater than 500 μmol·L^-1. The therapeutic index of TDF calculated by CC₅₀/EC₅₀ was greater than 18.20, which was significantly higher than that of ribavirin. The results suggest that TDF has good anti-ZIKV activity in vitro and is expected to become a candidate drug for anti-ZIKV therapy.

As a widely existing natural nanoparticle in living organisms, ferritin nanocage was proven to be a potential nanomaterial in the biomedical field, due to its excellent biocompatibility, specific active targeting properties, ease for preparation or modification, and unique self-assembly properties. This review presents an overview of ferritin nanocage in structural characteristics, surface modifications, and outlines its practical applications for drug delivery, medical imaging, as well as disease diagnosis or treatment. The researches of ferritin nanocage as drug carriers are classified and summarized in carrying different kinds of chemical components of drugs or nucleic acid according to different characteristics. Finally, the prospects in the development of ferritin nanocage are also outlined.

Mengla virus (MLAV), isolated from the bats in China, was identified as a new genus of filovirus in 2019, i.e. Dianlovirus genus of Filoviridae family. Among filoviruses, Ebola virus (EBOV) and Marburg virus (MARV) are the most contagious viruses with mortality rates of 24%-90%. Phylogenetic analysis showed that MLAV was closely related to MARV among the members of filovirus family. MLAV enters into host cells via viral glycoprotein (GP). The recombinant virus study indicated that MLAV has a potential for bat-to-human cross-species transmission. In this study, a GP-mediated MLAV entry evaluating model was established, and by using this model, we investigated the susceptibility of MLAV to the human cell lines sourced from different tissues and the African green monkey kidney cell lines. Four compounds, chloroquine, tetrandrine, clomiphene, and toremifene, which were known as EBOV and MARV entry blockers, were tested for HIV/MLAV-GP infection. It was found that chloroquine effectively blocked the entry of MLAV with the half maximal effective concentration (EC₅₀) of 1.56 μmol·L^-1, resembling its anti-EBOV and -MARV activities. To the best of our acknowledge, there is no anti-MLAV drug reported by far, and the identification of chloroquine as an MLAV entry inhibitor may provide an insight for developing anti-filovirus agents.

The traditional systemic treatment of post-traumatic stress disorder (PTSD) requires a long time period for an effect and has obvious side effects. In this study, tetrandrine temperature-sensitive gel (TTG) was prepared for treatment of PTSD in mice by nasal administration. TTG was prepared with poloxamer as matrix, the gelation temperature was suitable (< 32℃) and the gelation time was short (1.32 min). Rheology experiments demonstrated that TTG has temperature sensitivity. In vivo imaging system of small animals proved that TTG nasal cavity retention time was so long. The cilia toxic test of toad showed that the formulation was safe. Animal experiments were approved by the Ethics Committee of Beijing Institute of Radiation Medicine, Academy of Military Medical Sciences and the experiments were conducted in accordance with relevant guidelines and regulations. The mice were randomly assigned into healthy group, model group and TTG group. The PTSD model of mice was established by single prolonged stress (SPS) and foot-shock method to generate anxiety and fear behavior. On the day 0 of TTG administration, SPS model mice were evaluated by the elevated plus maze (EPM). Percentages of open arm entries number (OE), latency of open arm entries (OL) and the residence time of open arm entries (OT) all indicated that the SPS model was successfully established. On the 7th day of TTG administration, TTG increased the OE and OT, decreased the OL of SPS mice. The feard behavior of mice in the foot-shock model was tested using conditioned fear box, 7 days of TTG treatment can reduce the freezing time of the mice obviously. The pathological changes of hippocampus, prefrontal cortex and amygdala were observed by H & E histological sections and c-fos immunohistochemical expression. The main influenced areas of PTSD were revealed to be the CA1 of hippocampus, prefrontal cortex and amygdala. All of the above indicated that TTG is a convenient, safe and effective drug for PTSD treatment, and will provide a new choice for clinical management of PTSD.

In this paper, the lipidomics was used to analyze the changes to address how Uncaria interrupts lipid metabolism in the liver of spontaneously hypertensive rats, and to explore the mechanism of action of Uncaria. All the experiments were approved by the animal protection and use committee of Shandong University of Traditional Chinese Medicine. UHPLC-Q Extractive orbitrap high-resolution mass spectrometry was used to collect lipid metabolite information of the rat livers. Through pattern recognition, matters with noticeable differences were recognized. Mass spectrum and data base searching helped to identify the potential biomarkers. Pattern recognition results indicated that the rats from control versus SHR group showed clear differences. Compared with the rats from the control group, there are decreases in sphosphatidylcholine, phosphatidic acid, diacylglycerol and sphingomyelin in rats from the SHR group, however lysophosphatidylcholine, triglyceride, linoleic acid, arachidonic acid and ceramide are increased. Uncaria could regulate the disorder of lipid metabolism by interfering with glycerophospholipid, sphingolipid, linoleic acid, and arachidonic acid metabolic pathways. This study provided the mechanistic understanding of the impact of Uncaria on lipid metabolism and revealed the lipid metabolism pathways affected to offer the explanation for the complex mechanism of action.

Transforming growth factor-β (TGF-β) belongs to a group of biologically active cytokines that bind to its receptors to activate Smad signaling and non-Smad signaling pathways. The biological functions of TGF-β include promoting cell epithelial-mesenchymal transition, tissue fibrosis, angiogenesis and tumor immune evasion, as well as dual effects of cancer suppression and cancer promotion. Given the fact that the ligand-and receptors-mediated abnormal activation of TGF-β signaling pathways play an important role in the pathogenesis of multiple diseases such as malignant tumors and tissue fibrosis, more than a dozen small-molecule inhibitors have been developed to block the TGF-β signaling pathways, providing a novel method for controlling the development of these diseases. At present, pirfenidone, an inhibitor for TGF-β production, has been approved for treatment of idiopathic pulmonary fibrosis, while the inhibitors of TGFβRI/ALK5 for therapeutics of tumors or myelodysplastic syndromes, including LY2157299, EW-7197 and LY3200882, are in the phase Ⅰ to Ⅲ clinical trials, with additional ones inhibiting TGFβRs such as SB-431542, LY2109761, TP-0427736, and IN-1130 being in the preclinical phase. This paper reviews recent advances in research of small-molecule inhibitors targeting TGF-β and its receptors.

Deformation or failure of organs is the final stage involving fibrosis, caused by fibrous scars composed of excess extracellular matrix proteins. Cellular senescence means a stable stagnation state with no proliferation, during which the senescent cells maintain biochemical metabolism but promote excessive expression of extracellular matrix proteins due to secreting inflammatory factors, which contribute to the development of various organ fibrosis including myocardial fibrosis, and pulmonary fibrosis. It has been shown that both the incidence of organ fibrosis and the number of senescent cells increase with age. This review mainly summarizes mechanisms of cellular senescence and its contribution to the process of various organ fibrosis. Current anti-fibrotic drug therapy focused on cellular senescence is discussed. Cellular senescence has profound implications in the pathogenesis of fibrotic diseases and provides a new target for new effective treatments.

The long-term use of antibiotics in clinical practice leads to bacterial variation and resistance. In addition, the excessive or improper use of antibiotics in medical and agricultural fields increases the occurrence of bacterial resistance. In 2017, the World Health Organization has for the first time released a list of 12 bacteria or bacterial families that pose the greatest threat to human health and for which new antibiotics are desperately needed, and three quarters of them are Gram-negative bacteria. Gram-negative bacteria has multi-layered cell wall that prevents many antibiotics from accessing their targets. Therefore, it is very difficult to develop drugs against Gram-negative bacteria, no new class of antibiotic has been approved for Gram-negative pathogens in over fifty years. Here, we summarized recent advances in the study of new antibacterial agents with different mechanisms of action against Gram-negative pathogens.