The Chinese herbal prescription Yi-Fei San-Jie pill (YFSJ) has been used for adjuvant treatment in patients with lung cancer for a long time.
Reports have indicated that the combination of gefitinib ...(Gef) with YFSJ inhibits the proliferation of EGFR-TKI-resistant cell lines by enhancing cellular apoptosis and autophagy in non-small cell lung cancer (NSCLC). However, the molecular mechanisms underlying the effect of YFSJ on EGFR-TKI resistance and related metabolic pathways remain to be explored.
In our report, ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), metabolomics, network pharmacology, bioinformatics, and biological analysis methods were used to investigate the mechanism.
The UPLC-MS/MS data identified 42 active compounds of YFSJ extracts. YFSJ extracts can enhance the antitumor efficacy of Gef without hepatic and renal toxicity in vivo. The analysis of the metabolomics pathway enrichment revealed that YFSJ mainly affected the tyrosine metabolism pathway in rat models. Moreover, YFSJ has been shown to reverse Gef resistance and improve the effects of Gef on the cellular viability, migration capacity, and cell cycle arrest of NSCLC cell lines with EGFR mutations. The results of network pharmacology and molecular docking analyses revealed that tyrosine metabolism-related active compounds of YFSJ affect EGFR-TKIs resistance in NSCLC by targeting cell cycle and the MET/EGFR signaling pathway; these findings were validated by western blotting and immunohistochemistry.
YFSJ inhibits NSCLC by inducing cell cycle arrest in the G1/S phase to suppress tumor growth, cell viability, and cell migration through synergistic effects with Gef via the tyrosine metabolic pathway and the EGFR/MET signaling pathway. To summarize, the findings of the current study indicate that YFSJ is a prospective complementary treatment for Gef-resistant NSCLC.
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•The mechanism of Yi-Fei San-Jie pill in reducing epidermal growth factor receptor tyrosine kinase inhibitors resistance could be via its tyrosine metabolism-related antitumor compounds that regulate the MET/EGFR/CDK2 pathway involved in tyrosine metabolism, tumor growth inhibition, and cell cycle arrest in non–small cell lung cancer.•Various cyclins and cyclin-dependent kinases, including CDK2 and CDK4, regulate the cell cycle and the sensitivity to epidermal growth factor receptor tyrosine kinase inhibitors in cancer cells.•EGFR signaling is involved in cell cycle regulation and cell proliferation via the activation of cyclin-dependent kinases, such as CDK2 and CDK4.•Resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non–small cell lung cancer is associated with upregulation of MET signaling.
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•Reaction will start when the initial distance among participating reactants is shorter than the minimum initial distance of reaction that initiates reaction initialization through ...excellent physical interfacial contact.•2D distribution binning in the xy plane and the average bond length analysis based on ReaxFF MD trajectories reveal reaction characteristics and iron aluminides products.
Compared with organic-counterpart or micro-counterpart, nanothermites have attracted substantial interests owing to their exhibited outstanding properties. A common goal of a great amount of studies in nanothermite-based energetic materials is to enhance the reaction properties. Thermite planar geometry structural systems have been the promising structures because they are very tunable to control the alternating layered geometry and thickness of fuel and oxidizer. In this article, the planar interfacial contact Al/Fe2O3 nanolaminate thermite systems were studied to explore the effects of variations in preheating temperature, preheating rate and the initial distance between participating fuel and oxidizer on reaction properties and products characterizations by using the classic molecular dynamics simulations. According to the results, ignition delay and reaction time decrease with increasing the preheating temperature. The ignition delay and reaction time decrease from hundreds of picoseconds to a few tens of picoseconds. Additionally, higher heating rate results in higher energized structure, and much more energy was absorbed during heating period leading to a much shorter ignition delay. Reaction will start when the initial distance among reactants is shorter than a certain distance after passing through the ignition delay. Analyses also show the majority number of triangular structure for Fe2Al clusters and a small amount of tetrahedral structure for Fe3Al clusters during thermite reaction.
To study the consensuses on lung cancer treatment by Chinese medicine experts from North China and South China, and to analyze their medication features from viewpoints such as the medication ...frequency, combination laws, medication classification by collecting 800 recipes on the treatment of lung cancer patients prescribed by 8 Chinese oncologists from Guanganmen Hospital of China Academy of Chinese Medical Sciences, the Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, and Guangdong Provincial Hospital of Traditional Chinese Medicine. Results showed that coix seed, poria, pinelliae tuber were the three herbs most commonly used in treatment of lung cancer by all experts. They generally accepted Pi invigorating and phlegm removing method as the basic treatment method for treating lung cancer. Secondly, they usually used white peony root, heterophylla falsestarwort root, and ophiopogonis tuber, etc. (with higher medication frequency) to nourish yin and moisten Fei. Thirdly, consistenc
Objective
To observe the efficacy and the influence on quality of life (QOL) of syndrome differentiation treatment with Chinese medicine (CM) for opioid-induced constipation as well as the safety and ...influence on analgesic effect of opioids.
Methods
Totally 406 cases enrolled from 53 collaborating medical centers were randomly assigned to a CM group and a control group. The CM group were treated with CM decoction based on syndrome differentiation, and the control group were treated with Phenolphthalein Tablet. Both groups were treated for 14 days. Cleveland constipation score (CCS), numerical rating scale (NRS) of pain and Chinese version of European Organisation for Research and Treatment of Cancer, Quality of Life Questionnaire-C30 V3.0 (EORTC QLQ-C30 V3.0) were used to evaluate the efficacy, pain controlled and QOL status.
Results
The comparisons of CCS score reduction and QOL between the two groups after treatment suggested that the improvements of constipation and QOL in the CM group were better than that in the control group (
P
<0.05). The total efficiency of the CM group was better than the control group (93.5% vs. 86.4%,
P
<0.05). There was no significant difference in NRS scores between before and after treatment in both groups. There was no serious drug-related adverse event during the course of study.
Conclusion
CM decoction could effectively treat opioid-induced constipation and improve patients’ QOL at the same time. It is safe and doesn’t affect the analgesic effect of opioids when treating constipation.
The extracellular matrix is the main component of the tumor microenvironment. Extracellular matrix remodels with the oncogenesis and development of tumors. Previous studies usually focused on the ...changes of proteins in normal colorectal tissues and colorectal cancers. Little is known about the changes in the extracellular matrix in different stages of colorectal cancer and the effects of these changes on the development of this cancer.
To test the changes of type I collagen, type IV collagen, matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinase-3 (TIMP-3) in different stages of colorectal cancer and the effects of these changes on the proliferation of cancer cells.
The extracellular matrix from various stages of colorectal cancer and normal colon tissue was obtained by using acellular technology. We used proteomics to detect the differential expression of proteins between normal colon tissues and colorectal cancer tissues, and then we used Western blot to observe their expression in each stage of colorectal cancer and in normal colon tissue. By co-culturing the extracellular matrix and HT29 colon cancer cells
and
, we tested the cancer cell proliferation rate
by methyl thiazolyl tetrazolium (MTT) assay and
by measuring the tumor volume.
The expression of type I collagen and MMP-2 increased with increased tumor stage. The expression of MMP-9 was higher in colorectal cancer tissues and was highest in stage III cancer. The expression of type IV collagen and TIMP-3 decreased with increased tumor stage. The proliferation rate of cancer cells in the extracellular matrix of colorectal cancer was higher than that in the extracellular matrix of the normal colon.
These data suggest that the extracellular matrix structure and composition become disorganized during the development of tumors, which is more conducive for the growth of cancer cells.
To investigate the effects of Yiqi Chutan Recipe (YCR, a Chinese herbal prescription for invigorating qi and removing phlegm) on the growth and metastasis of tumor, survival time, and the expressions ...of peroxiredoxin (PRDX-1 and PRDX-6) in tumor tissue of C57BL/6J mice bearing Lewis lung carcinoma.
Lewis lung carcinoma cells were transplanted to 90 C57BL/6J mice receiving preconditioning for inducing Pi-deficiency syndrome and divided into three groups treated respectively with saline, high dose YCR (3.0 g/kg) and low dose YCR (1.0 g/kg) once a day via gastric infusion. Besides, a group of 30 healthy mice simply received tumor cell transplantation was set up for controls. Ten mice selected from each group were sacrificed 21 days later, the size, weight and lung metastasis foci of tumor in mice were measured, and expressions of PRDX-1 and PRDX-6 in tumor tissue were detected using immunohistochemical method. The survival time of the remained 20 mice in each groups was observed.
Tumor size, weight and the numbe
The purification, renewal and differentiation of native cardiac progenitors would form a mechanistic underpinning for unravelling steps for cardiac cell lineage formation, and their links to forms of ...congenital and adult cardiac diseases. Until now there has been little evidence for native cardiac precursor cells in the postnatal heart. Herein, we report the identification of isl1+ cardiac progenitors in postnatal rat, mouse and human myocardium. A cardiac mesenchymal feeder layer allows renewal of the isolated progenitor cells with maintenance of their capability to adopt a fully differentiated cardiomyocyte phenotype. Tamoxifen-inducible Cre/lox technology enables selective marking of this progenitor cell population including its progeny, at a defined time, and purification to relative homogeneity. Co-culture studies with neonatal myocytes indicate that isl1+ cells represent authentic, endogenous cardiac progenitors (cardioblasts) that display highly efficient conversion to a mature cardiac phenotype with stable expression of myocytic markers (25%) in the absence of cell fusion, intact Ca2+-cycling, and the generation of action potentials. The discovery of native cardioblasts represents a genetically based system to identify steps in cardiac cell lineage formation and maturation in development and disease.
Traditional Chinese medicine (TCM) is an important part of the treatment of primary liver cancer (PLC) in China; however, the current instructions for the integrative use of traditional Chinese and ...Western medicine for PLC are mostly based on expert opinion. There is no evidence-based guideline for clinical practice in this field. Therefore, the Shanghai Association of Chinese Integrative Medicine has established a multidisciplinary working group to develop this guideline, which focuses on the most important questions about the use of TCM during PLC treatment. This guideline was developed following the methodological process recommended by the World Health Organization Handbook for Guideline Development. Two rounds of questionnaire survey were performed to identify clinical questions; published evidence was searched; the Grading of Recommendations Assessment, Development and Evaluation approach was used to evaluate the body of evidence; and recommendations were formulated by combining the quality of evidence, patient preferences and values, and other risk factors. The guideline was written based on the Reporting Items for Practice Guidelines in Healthcare tool. This guideline contains 10 recommendations related to 8 questions, including recommendations for early treatment by TCM after surgery, TCM combined with transcatheter arterial chemoembolization for advanced PLC, TCM drugs for external use, and acupuncture and moxibustion therapy.
This paper describes the development of the Chinese Quality of Life Instrument (ChQOL) which is a self-report health status instrument. Chinese Medicine relies very much on asking subjective feelings ...of patients in the process of diagnosis and monitoring of treatment. For thousands of years, Chinese Medicine practitioners have accumulated a good wealth of experiences in asking questions about health of their patients based on the concept of health in Chinese Medicine. These experiences were then transformed into questions for the ChQOL. It is believed that ChQOL can contribute to the existing Patient Report Outcome measures. This paper outlines the concept of health and disease in Traditional Chinese Medicine, the building of the conceptual framework of the ChQOL, the steps of drafting, selecting and validating the items, and the psychometric properties of the ChQOL.
The development of the ChQOL was based on the concept of health in Traditional Chinese Medicine with a theory driven approach. Based on the results of literature review, the research team developed an initial model of health which encompassed the concept of health in TCM. An expert panel was then invited to comment and give suggestions for improvement of the initial model. According to their suggestions, the model was refined and a set of initial items for the ChQOL was drafted. The refined model, together with the key domains, facets and initial items of the ChQOL were then mailed to a sample of about 100 Chinese medicine practitioners throughout Mainland China for their comments and advice. A revised set of items were developed for linguistic testing by a convenience sample consisting of both healthy people and people who attended Chinese Medicine treatment. After that, an item pool was developed for field-testing. Field test was conducted on a convenience sample of healthy and patient subjects to determine the construct validity and psychometric properties of the ChQOL.
Construct validity was established by various methods, i.e. the internal consistency in all facets and domains were good; the correlation between facets to domain, and domains to overall ChQOL correlation were high; confirmatory factor analysis showed that the structure fitness of all facets, domain and overall structure were good with CFI > 0.9. Test-retest reliability was also good, especially in the domain scores with ICC value ranging from 0.83 to 0.90. No ceiling or floor effect was noted which indicated that ChQOL can be applied to subjects with a wide range of health status. Most facet scores, domain scores and the overall CHQOL scores were able to discriminate groups of subjects with known differences in health status. The ChQOL had mild positive convergence with the other generic health related QOL measures, i.e. the WHOQOL-100 and the SF-36, with moderate correlations.
In conclusion, the study indicated that the ChQOL is conceptually valid with satisfactory psychometric properties. It can provide additional information on health and QOL on top of the existing generic health related QOL measures. Furthermore, it forms basis for further testing and applications in clinical trials.
The pseudo-rapidity distributions of the charged particles produced in the asymmetric collision systems p+Al, p+Au and
3
He+Au at
s
NN
=
200
GeV are evaluated in the framework of a fireball model ...with Tsallis thermodynamics. The fireball model assumes that the experimentally measured particles are produced by fireballs following the Tsallis distribution and it can effectively describe the experimental data. Our results as well as previous results for d+Au collisions at
s
NN
=
200
GeV and p+Pb collisions at
s
NN
=
5.02
TeV validate that the fireball model based on Tsallis thermodynamics can provide a universal framework for pseudo-rapidity distribution of the charged particles produced in asymmetric collision systems. We predict the centrality dependence of the total charged particle multiplicity in the p+Al, p+Au and
3
He+Au collisions. Additionally, the dependences of the fireball model parameters (
y
0
a
,
y
0
A
,
σ
a
and
σ
A
) on the centrality and system size are studied.
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