RESUMEN
The classical famous prescription Dajianzhong Decoction is recorded in Synopsis of the Golden Chamber written by Zhang Zhongjing in the Eastern Han Dynasty. It has a long history and definite clinical effects, while this prescription has not been manufactured into Chinese patent medicine preparation. We collected many ancient books of traditional Chinese medicine(TCM) by using the method of bibliometrics and got 211 valid data terms which involved 67 ancient books. The history, main treated syndromes, formulation principle, origins and processiong of medicinal materials, and decoction method of Dajianzhong Decoction were analyzed. Despite the different views of various generations of medical experts toward the composition of this prescription, the compatibility ratio of Ginseng Radix et Rhizoma to Zingiberis Rhizoma Recens is constant. Furthermore, we explored the origins of synonyms of Dajianzhong Decoction. On the basis of this study, we hope to gain an insight into the research and development of the compound preparations of Dajianzhong Decoction and provide reference for the heritage and innovation of other classical prescriptions.
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Medicamentos Herbarios Chinos , Medicina Tradicional China , Prescripciones , RizomaRESUMEN
Non-small-cell lung cancer (NSCLC) remains the most common malignancy with the highest morbidity and mortality worldwide. In our previous study, we found that a classic traditional Chinese medicine (TCM) formula Ze-Qi-Tang (ZQT), which has been used in the treatment of respiratory diseases for thousands of years, could directly inhibit the growth of human NSCLC cells via the p53 signaling pathway. In this study, we explored the immunomodulatory functions of ZQT. We found that ZQT significantly prolonged the survival of orthotopic lung cancer model mice by modulating the tumor microenvironment (TME). ZQT remarkably reduced the number of MDSCs (especially G-MDSCs) and inhibited their immunosuppressive activity by inducing apoptosis in these cells via the STAT3/S100A9/Bcl-2/caspase-3 signaling pathway. When G-MDSCs were depleted, the survival promotion effect of ZQT and its inhibitory effect on lung luminescence signal disappeared in tumor-bearing mice. This is the first study to illustrate the immunomodulatory effect of ZQT in NSCLC and the underlying molecular mechanism.
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Apoptosis/efectos de los fármacos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Granulocitos/efectos de los fármacos , Neoplasias Pulmonares/tratamiento farmacológico , Medicina Tradicional China , Células Supresoras de Origen Mieloide/efectos de los fármacos , Animales , Calgranulina B/fisiología , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Caspasa 3/fisiología , Línea Celular Tumoral , Medicamentos Herbarios Chinos/uso terapéutico , Granulocitos/patología , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Ratones , Ratones Endogámicos C57BL , Células Supresoras de Origen Mieloide/patología , Proteínas Proto-Oncogénicas c-bcl-2/fisiología , Factor de Transcripción STAT3/fisiología , Transducción de Señal/efectos de los fármacos , Microambiente TumoralRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: The traditional Chinese medicine (TCM) Tian-Men-Dong decoction (TD) has been able to effectively treat lung cancer in China for thousands of years. TD improves the quality of life in lung cancer patients by promoting nourishment of yin and reducing dryness, clearing the lung and removing toxins. Pharmacological studies show that TD contains active antitumour ingredients, but its underlying mechanism remains unknown. AIM OF THE STUDY: This study aims at exploring potential mechanisms of TD in the treatment of lung cancer by regulating granulocytic-myeloid-derived suppressor cells (G-MDSCs). MATERIALS AND METHODS: An orthotopic lung cancer mouse model was generated by intrapulmonary injection with LLC-luciferase cells in immunocompetent C57BL/6 mice or immunodeficient nude mice. TD/saline was orally administered once to the model mice daily for 4 weeks. Live imaging was conducted to monitor tumour growth. Immune profiles were detected by flow cytometry. H&E and ELISA were applied to test the cytotoxicity of the TD treatment. RT-qPCR and western blotting were performed to detect apoptosis-related proteins in G-MDSCs. A neutralizing antibody (anti-Ly6G) was utilized to exhaust the G-MDSCs via intraperitoneal injection. G-MDSCs were adoptively transferred from wild-type tumour-bearing mice. Immunofluorescence, TUNEL and Annexin V/PI staining were conducted to analyse apoptosis-related markers. A coculture assay of purified MDSCs and T cells labelled with CFSE was performed to test the immunosuppressive activity of MDSCs. The presence of TD/IL-1ß/TD + IL-1ß in purified G-MDSCs cocultured with the LLC system was used for ex vivo experiments to detect IL-1ß-mediated apoptosis of G-MDSCs. RESULTS: TD prolonged the survival of immune competent C57BL/6 mice in an orthotopic lung cancer model, but did not have the same effect in immunodeficient nude mice, indicating that its antitumour properties of TD are exerted by regulating immunity. TD induced G-MDSC apoptosis via the IL-1ß-mediated NF-κB signalling cascade leading to effectively weaken the immunosuppressive activity of G-MDSCs and promote CD8+ T-cell infiltration, which was supported by both the depletion and adoptive transfer of G-MDSCs assays. In addition, TD also showed minimal cytotoxicity both in vivo and in vitro. CONCLUSION: This study reveals for the first time that TD, a classic TCM prescription, is able to regulate G-MDSC activity and trigger its apoptosis via the IL-1ß-mediated NF-κB signalling pathway, reshaping the tumour microenvironment and demonstrating antitumour effects. These findings provide a scientific foundation the clinical treatment of lung cancer with TD.
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Neoplasias Pulmonares , Células Supresoras de Origen Mieloide , Ratones , Animales , Ratones Desnudos , FN-kappa B/metabolismo , Calidad de Vida , Ratones Endogámicos C57BL , Neoplasias Pulmonares/metabolismo , Inmunosupresores/farmacología , Microambiente TumoralRESUMEN
Bacillary dysentery is an infectious disease caused by Shigella dysenteriae, which has a seasonal distribution. External environmental factors, including climate, play a significant role in its transmission. This paper identifies climate-related risk factors and their role in bacillary dysentery transmission. Harbin, in northeast China, with a temperate climate, and Quzhou, in southern China, with a subtropical climate, are chosen as the study locations. The least absolute shrinkage and selectionator operator is applied to select relevant climate factors involved in the transmission of bacillary dysentery. Based on the selected relevant climate factors and incidence rates, an AutoRegressive Integrated Moving Average (ARIMA) model is established successfully as a time series prediction model. The numerical results demonstrate that the mean water vapour pressure over the previous month results in a high relative risk for bacillary dysentery transmission in both cities, and the ARIMA model can successfully perform such a prediction. These results provide better explanations for the relationship between climate factors and bacillary dysentery transmission than those put forth in other studies that use only correlation coefficients or fitting models. The findings in this paper demonstrate that the mean water vapour pressure over the previous month is an important predictor for the transmission of bacillary dysentery.
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Disentería Bacilar/transmisión , Presión del Aire , China/epidemiología , Humanos , Modelos Teóricos , Factores de Riesgo , Estaciones del Año , VaporRESUMEN
BACKGROUND: Panax Notoginseng flower saponins (PNFS) are the main active component of Panax notoginseng (Burk) F. H. Chen flower bud (PNF) and possess significant anti-inflammatory efficacy. This study aims to explore the mechanisms underlying PNFS' antiflammatory action in RAW264.7 macrophages. METHODS: A cell counting kit-8 assay was used to determine the viability of RAW264.7 macrophages. Anti-inflammation effects of PNFS in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages were measured based on the detection of nitric oxide (NO) overproduction (Griess method, DAF-FM DA fluorescence assay and NO2 (-) scavenging assay), and interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha gene overexpression (real-time PCR and ELISA). Inducible nitric oxide synthase (iNOS) gene overexpression was determined by real-time PCR and western blotting. iNOS enzyme activity was also assayed. The mechanisms underlying the suppression of iNOS gene overexpression by PNFS were explored using real-time PCR and western blotting to assess mRNA and protein levels of components of the Toll-like receptor 4 mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K)/Akt, and nuclear factor-kappa B (NF-kappa B) signaling pathways. RESULTS: PNFS (50, 100, 200 µg/mL) significantly reduced LPS-induced overproduction of NO (P < 0.001, P < 0.001, P < 0.001) and IL-6 (P = 0.103, P < 0.001, P < 0.001), but did not affect TNF-alpha overproduction. PNFS (50, 100, 200 µg/mL) also markedly decreased LPS-activated iNOS (P < 0.001, P < 0.001, P < 0.001) and TLR4 gene overexpression (P = 0.858, P = 0.046, P = 0.005). Furthermore, treatment with PNFS (200 µg/mL) suppressed the phosphorylation of MAPKs including P38 (P = 0.001), c-Jun N-terminal kinase (JNK) (P = 0.036) and extracellular-signal regulated kinase (ERK) 1/2 (P = 0.021). PNFS (200 µg/mL) inhibited the activation of the NF-kappa B signaling pathway by preventing the phosphorylation of inhibitor of NF-kappa B alpha (I-kappa B alpha) (P = 0.004) and P65 (P = 0.023), but PNFS (200 µg/mL) could not activate the LPS-induced PI3K-Akt signaling pathway. CONCLUSIONS: PNFS significantly down-regulated iNOS gene overexpression and thereby decreased NO overproduction via the inhibition of TLR4-mediated MAPK/NF-kappa B signaling pathways, but not the PI3K/Akt signaling pathway.