AIM To study endophytic fungi from Scutellaria baicalensis Georgi.and the enzyme inhibitory activities of their secondary metabolites.METHODS Six different media were used to isolate and purify endophytic fungi from S.baicalensis by tissue homogenate method.The activities of secondary metabolites were evaluated by targeting different enzymes.The highly active strains were identified by molecular biology combined with morphology,and the highly active chemical components were tracked and separated by modern chromatographic separation technology.RESULTS Sixty-four endophytic fungal strains were isolated from S.baicalensis,and one hundred and twenty-eight secondary metabolites were obtained by fermentation.The samples with certain inhibitory activities against adenosine deaminase(ADA),β-lactamase and tyrosinase(TYR)accounted for 14.06%,3.91%and 18.75%,respectively.Strain HTS-23-2 showed high TYR inhibitory activity,and 99%homology with Aspergillus flavus by molecular identification.One compound was isolated from the fermentation samples and identified as kojic acid.CONCLUSION S.baicalensis harbors a rich diversity of endophytic fungi,which serve as a valuable resource for active substances.

Immune checkpoints (ICs) are immunosuppressive molecules expressed on immune cells, which can regulate immune cells' activation. Immune checkpoint inhibitors (ICIs) which can block the interaction of immune checkpoints and their ligands, improve the cytotoxic effect of the immune system on tumor cells. Immunotherapy such as employing ICIs has gradually become a conventional therapeutic strategy for cancer treatment. However, the low response rate and the emergence of drug resistance have seriously affected the clinical efficacy of ICIs. Reactive oxygen species (ROS) are electronic reduction products of active oxygen, as well as natural by-products of cell metabolism, which can be used as regulators of intercellular signals. Tumor microenvironment (TME) is often in the state of oxidative stress (OS), which is the imbalance between oxidative system and antioxidant system. ROS can affect the interaction with its ligands by regulating the expression and activity of immune checkpoints in TME, thus affecting the anti-tumor effect of immune cells. Accumulating studies have shown that ROS could regulate tumor immune checkpoints through several pathways. Due to different types and stages of tumor, it would be clinical beneficial to understand the mechanistic link of ROS on tumor immune checkpoint, and choose appropriate ROS regulators combined with immune checkpoint inhibitors to maximize anti-tumor effects. This article reviews the common metabolic sources and characteristics of ROS, the regulatory effect and mechanism of ROS on tumor immune checkpoints and its therapeutic application.

Breast cancer is currently one of the caneers with the highest incidence.Clinically, most breast eaneer patients often die due to distant metastasis.In the complex easeade of metasta¬sis, the formation of the pre-metastasis niche ( PMN) has been considered to he cnrcial in the process of distant metastasis of tumors in recent years.Tumors at the primary site secrete tumor- derived secretory factors (TDSF) , extracellular vesicles ( EV) and so on to metastasize target organs.thereby changing the mi- croenvironment of the target organs to adapt to the subsequent distant metastasis of the tumor.Breast cancer is a kind of cancer number of studies have revealed the mechanism of the breast cancer pre-metastatic niche, showing that inhibiting the PMN can reduce breast cancer metastasis.The multi-target and multi- component features of traditional Chinese medicine have been re¬ported to effectively interfere with the formation of PMN.This review summarizes the breast cancer's mechanism of lung pre- metastatic niche formation and traditional Chinese medicine in¬tervention.

OBJECTIVE: To investigate the expression of ROBO3 in pediatric AML patients and explore its function on cell proliferation and apoptosis. METHODS: The expression of ROBO3 in pediatric AML patients at different treatment stage was detected by real-time quantitative polymerase chain reaction (RT-qPCR). The relationship between the expression of ROBO3 and clinic pathological characteristics in newly diagnosed pediatric AML patients was analyzed. Moreover, the effects of ROBO3 on the proliferation and apoptosis of AML cell lines HL-60 and THP-1 were estimated by using CCK-8 and flow cytometry after transfection with ROBO3 siRNA. RESULTS: It was found that ROBO3 expression was significantly increased in most of newly diagnosed pediatric AML patients, especially in non-M3 subtype, younger patients (<10 years old), and high risk group, compared to corresponding controls. Furthermore, the expression level of ROBO3 was sharply decreased in patients who achieved complete remission. Targeting ROBO3 significantly inhibited AML cell proliferation, as well as increased apoptosis by ROBO3 siRNA transfection in vitro. CONCLUSION ROBO3 is differentially expressed within distinct subtypes of the pediatric AML patients, which suggested that ROBO3 may be a potential biomarker and a new therapeutic target for pediatric AML.
Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Child ; Humans ; Leukemia, Myeloid, Acute/genetics* ; MicroRNAs/genetics* ; RNA, Small Interfering ; Receptors, Cell Surface ; Sincalide

Aim To explore the effect of THPA1 in the metasta- sis of gastric cancer and the underlying mechanism. Methods The correlation between TRPA1 and the survival time of gastric cancer patients was analyzed using Kaplan-Meier plotter data base. The expressions of TRPA1 in different cells were detected by Western blot. Docking was used to explore the binding poten tial between cardamonin and TRPA1. Long-term dynamic cell imaging, CCK-8 and Transwell were used to evaluate the effects of HC-030031 and cardamonin on the proliferation and migration of MKN-45 cells. The differential metabolites between normal gastric epithelial cells and gastric cancer cells were studied by GC-MS. Results The expression of TRPA1 in gastric cancer patients was significantly negatively correlated with their surviv al. TRPA1 was overexpressed in gastric cancer cells. And the migration of gastric cancer cells was positively correlated with the expression and activation of TRPA1. Cardamonin had similar pharmacological effects with HC-030031, both of which could reduce the migration of gastric cancer cells. The metabolic path ways of asparagine and myo-inositol were found to be different between gastric cancer cells and normal gastric epithelial cells by cell metabolomics analysis. Conclusions TRPAI may be an indicator for detecting gastric cancer metastasis. Cardamonin in hibits metastasis by binding to TRPAI, meanwhile restrains the activation of TRPAI. Cardamonin may inhibit the function of TRPAI by binding to TRPAI, playing a role in inhibiting gastric cancer metastasis.

; β-adrenergic receptors (β-ARs) are widely found in organs of the human body and play an important role in regulating heart function, blood vessel dilation, energy metabolism, etc. Studies have shown that β-ARs are abnormally high in breast cancer cells, which can promote the occurrence and development of breast cancer by affecting the growth and metabolism of breast cancer, invasive metastasis, and angiogenesis. Clinical studies have shown that blocking β-ARs signaling improves the prognosis of breast cancer patients, so β-ARs may be a potential treatment target for breast cancer. This paper summarizes the role of β-ARs in the development of breast cancer, with a view to providing some reference for follow-up research and clinical treatment.

Background:Transcranial alternating current stimulation (tACS) offers a new approach for adult patients with major depressive disorder (MDD).The study is to evaluate the efficacy and safety of tACS treating MDD.Methods:This is an 8-week,double-blind,randomized,placebo-controlled study.Ninety-two drug-naive patients with MDD aged 18 to 65 years will receive 20 daily 40-min,77.5-Hz,15-mA sessions of active or sham tACS targeting the forehead and both mastoid areas on weekdays for 4 consecutive weeks (week 4),following a 4-week observation period (week 8).The primary outcome is the remission rate defined as the 17-item Hamilton depression rating scale (HDRS-17) score ≤7 at week 8.Secondary outcomes are the rates of response at weeks 4 and 8 and rate of remission at week 4 based on HDRS-17,the proportion of participants having improvement in the clinical global impression-improvement,the change in HDRS-17 score (range,0-52,with higher scores indicating more depression) over the study,and variations of brain imaging and neurocognition from baseline to week 4.Safety will be assessed by vital signs at weeks 4 and 8,and adverse events will be collected during the entire study.Discussion:The tACS applied in this trial may have treatment effects on MDD with minimal side effects.

To systemically evaluate the benefits and side effects of Shensong Yangxin Capsules( SYC) in the adjuvant treatment of stable angina pectoris( SAP). Chinese and English databases( PubMed,EMbase,the Cochrane Library,CBM,CNKI,VIP,Wan Fang database) were retrieved to collect the randomized controlled trials( RCTs) about therapeutic efficacy of SYC combined with routine drug( trial group) vs routine drug( control group) in the treatment of SAP. The methodological quality of the RCTs was evaluated based on the cochrane risk of bias assessment tool. The data were extracted and Meta-analyzed by Reviewer Manager 5. 3. TSA 0. 9 software was used for trial sequential analysis( TSA) of the total effective rate of symptoms improvement. A total of 15 RCTs with 1 316 participants were included. RESULTS:: of Meta-analysis showed that the total effective rate of angina symptoms improvement( RR = 1. 15,95% CI[1. 09,1. 21],P<0. 001) of trial group were significantly higher than those of control group,with statistical significance,the total effective rate of electrocardiograms( ECG) improvement( RR = 1. 10,95% CI[0. 94,1. 29],P = 0. 25) of trial group were significantly higher than those of control group,but the difference was not statistically significant. After treatment,the improvement of the total time of 24 h general ischemia( SMD =-1. 21,95%CI[-1. 97,-0. 45],P = 0. 002),the ST-segment depression amplitude( SMD =-1. 30,95%CI [-1. 52,-1. 09],P<0. 001),the duration of angina pectoris attack( SMD =-1. 16,95% CI[-1. 36,-0. 95],P< 0. 001),the angina pectoris attack every week( SMD =-0. 80,95%CI[-1. 10,-0. 50],P<0. 001),the onsumption of nitroglycerin every week( SMD=-0. 72,95%CI[-1. 05,-0. 39],P<0. 001) in the trial group were better than that of the control group,and the difference was statistically significant. Besides,the improvement of the blood lipid and high sensitivity C reactive protein( hs-CRP) in the trial group were better than those of the control group after treatment,and the difference was statistically significant( P< 0. 001). Funnel plots and Egger's linear regression showed that there was no publication bias. By sensitivity analysis,it showed that the results of this study were stable and reliable. No obvious adverse drug reactions were observed in all studies. TSA analysis showed that the evidence of Meta-analysis was reliable. SYC combined with routine Western medicine treatment for SAP can improve the total effective rate of angina pectoris,reduce 24 h total ischemia time,ST segment depression amplitude,duration of angina pectoris attack,frequency of angina pectoris attack and nitroglycerin dosage,and also can improve blood lipid and hs-CRP levels.
Adjuvants, Pharmaceutic ; Angina, Stable ; drug therapy ; C-Reactive Protein ; analysis ; Capsules ; Drugs, Chinese Herbal ; therapeutic use ; Electrocardiography ; Humans ; Lipids ; blood ; Randomized Controlled Trials as Topic

OBJECTIVETo establish a domestic database of Enterobacteria cloacae (E. cloacae), and improve the identification efficiency using peptide mass fingerprinting.

METHODSPeptide mass fingerprinting was used for the identification and subtyping of E. cloacae. Eighty-seven strains, identified based on hsp60 genotyping, were used to construct and evaluate a new reference database.

RESULTSCompared with the original reference database, the identification efficiency and accuracy of the new reference database was greatly improved at the species level. The first super reference database for E. cloacae identification was also constructed and evaluated. Based on the super reference database and the main spectra projection dendrogram, E. cloacae strains were divided into two clades.

CONCLUSIONPeptide mass fingerprinting is a powerful method to identify and subtype E. cloacae, and the use of this method will allow us to obtain more information to understand the heterogeneous organism E. cloacae.

Objective To investigate the effect of fibronectin type Ⅲ and SPRY domain containing 1 (FSD1) protein on the invasion of glioma stem cells (GSCs), so as to probe into the new biomarkers or potential therapeutic targets for gliomas. Methods The Cancer Genome Altas (TCGA) database data were used to analyze and compare the FSD1 gene expression (the FSD1 mRNA level) in the glioblatoma (also known as glioblastoma multiforme, GBM) and normal brain tissues as well as in the different grade glioma tissues, and the correlation of the FDS1 gene expression (mRNA level) with the survival prognosis of patients was also analyzed using the TCGA database data. The lentivirus was used to overexpress the FSD1 protein in the GSCs, T4121 and D456. The effect of the overexpressed FSD1 protein on the invasive ability of the GSCs, T4121 and D456 was evaluated by Transwell invasion assay. Results The FSD1 gene expression (mRNA level) was significantly lower in GBM than in normal brain (P＜0.01). The FSD1 gene expression (the mRNA level) in gliomas significantly decreased with the increase of the gliomas grade (gradeⅡvs Ⅲ, P＜0.05;gradeⅢvs Ⅳ, P＜0.01). The survival prognosis of patients with gilomas was well associated with the level of FSD1 gene expression (the FSD1 mRNA level), as indicated by the overall survival rate of the patients, which was significantly lower in the patients with the low FSD1 mRNA level than in the patients with the high FSD1 mRNA level (P＜0.01). In the Transwell invasion assay, the count of the invasive cell numbers significantly decreased in the FSD1 protein-overexpressed T421 and D456 groups than in the corresponding control group (P＜0.01 in both T4121 and D456 cell lines). Conclusion There is a clinical relevance of the FSD1 expression for the malignant progression of gliomas (the grade of gliomas). The low level FSD1 is favorable for keeping the invasive ability in GSCs.