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1.
Front Neurosci ; 18: 1330594, 2024.
Article in English | MEDLINE | ID: mdl-38426019

ABSTRACT

Background: Many studies have investigated the efficacy of acupuncture in treating depression, but the mechanism of acupuncture for depression is still controversial and there is a lack of meta-analysis of mechanisms. Consequently, we investigated acupuncture's efficacy and mechanism of depression. Methods: We searched the Cochrane Library, PubMed, EMBASE, Web of Science. The SYRCLE Risk of Bias Tool was used to assess bias risk. Meta-analysis was performed using Stata 15.0 for indicators of depression mechanisms, body weight and behavioral tests. Results: A total of 22 studies with 497 animals with depressive-like behaviors were included. Meta-analysis showed that acupuncture significantly increased BDNF [SMD = 2.40, 95% CI (1.33, 3.46); I2 = 86.6%], 5-HT [SMD = 2.28, 95% CI (1.08, 3.47); I2 = 87.7%] compared to the control group (p < 0.05), and significantly reduced IL-1ß [SMD = -2.33, 95% CI (-3.43, -1.23); I2 = 69.6%], CORT [SMD = -2.81, 95% CI (-4.74, -0.87); I2 = 86.8%] (p < 0.05). Acupuncture improved body weight [SMD = 1.35, 95% CI (0.58, 2.11); I2 = 84.5%], forced swimming test [SMD = -1.89, 95% CI (-2.55, -1.24); I2 = 76.3%], open field test (crossing number [SMD = 3.08, 95% CI (1.98, 4.17); I2 = 86.7%], rearing number [SMD = 2.53, 95% CI (1.49, 3.57); I2 = 87.0%]) (p < 0.05) compared to the control group. Conclusion: Acupuncture may treat animals of depressive-like behaviors by regulating neurotrophic factors, neurotransmitters, inflammatory cytokines, neuroendocrine system. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023403318, identifier (CRD42023403318).

2.
Lab Invest ; 104(2): 100306, 2024 02.
Article in English | MEDLINE | ID: mdl-38104864

ABSTRACT

Immunocheckpoint inhibitors have shown impressive efficacy in patients with colon cancer and other types of solid tumor that are mismatch repair-deficient (dMMR). Currently, PCR-capillary electrophoresis is one of the mainstream detection methods for dMMR, but its accuracy is still limited by germline mismatch repair (MMR) mutations, the functional redundancy of the MMR system, and abnormal methylation of MutL Homolog 1 promoter. Therefore, this study aimed to develop new biomarkers for dMMR based on artificial intelligence (AI) and pathologic images, which may help to improve the detection accuracy. To screen for the differential expression genes (DEGs) in dMMR patients and validate their diagnostic and prognostic efficiency, we used the expression profile data from the Cancer Genome Atlas (TCGA). The results showed that the expression of Immunoglobulin Lambda Joining 3 in dMMR patients was significantly downregulated and negatively correlated with the prognosis. Meanwhile, our diagnostic models based on pathologic image features showed good performance with area under the curves (AUCs) of 0.73, 0.86, and 0.81 in the training, test, and external validation sets (Jiangsu Traditional Chinese Medicine Hospital cohort). Based on gene expression and pathologic characteristics, we developed an effective prognosis model for dMMR patients through multiple Cox regression analysis (with AUC values of 0.88, 0.89, and 0.88 at 1-, 3-, and 5-year intervals, respectively). In conclusion, our results showed that Immunoglobulin Lambda Joining 3 and nucleus shape-related parameters (such as nuclear texture, nuclear eccentricity, nuclear size, and nuclear pixel intensity) were independent diagnostic and prognostic factors, suggesting that they could be used as new biomarkers for dMMR patients.


Subject(s)
Adenocarcinoma , Brain Neoplasms , Colonic Neoplasms , Colorectal Neoplasms , Neoplastic Syndromes, Hereditary , Humans , Colonic Neoplasms/diagnosis , Colonic Neoplasms/genetics , Adenocarcinoma/diagnosis , Adenocarcinoma/genetics , Adenocarcinoma/pathology , DNA Mismatch Repair/genetics , Artificial Intelligence , Multiomics , Colorectal Neoplasms/pathology , Biomarkers , Immunoglobulins/genetics
3.
Huan Jing Ke Xue ; 44(6): 3619-3626, 2023 Jun 08.
Article in Chinese | MEDLINE | ID: mdl-37309976

ABSTRACT

Applying machine learning methods to resolve the cadmium (Cd) uptake characteristics of regional soil-wheat systems can contribute to the accuracy and rationality of risk decisions. Based on a regional survey, we constructed a Freundlich-type transfer equation, random forest (RF) model, and neural network (BPNN) model to predict wheat Cd enrichment factor (BCF-Cd); verified the prediction accuracy; and assessed the uncertainty of different models. The results showed that both RF (R2=0.583) and BPNN (R2=0.490) were better than the Freundlich transfer equation (R2=0.410). The RF and BPNN were further trained repeatedly, and the results showed that the mean absolute error (MAE) and root mean square error (RMSE) of RF and BPNN were close to each other. Additionally, the accuracy and stability of RF (R2=0.527-0.601) was higher than that of BPNN (R2=0.432-0.661). Feature importance analysis showed that multiple factors led to the heterogeneity of wheat BCF-Cd, in which soil phosphorus (P) and zinc (Zn) were the key variables affecting the change in wheat BCF-Cd. Parameter optimization can further improve the accuracy, stability, and generalization ability of the model.


Subject(s)
Cadmium , Triticum , Machine Learning , Phosphorus , Soil
4.
Huan Jing Ke Xue ; 44(2): 984-990, 2023 Feb 08.
Article in Chinese | MEDLINE | ID: mdl-36775621

ABSTRACT

The interaction of zinc (Zn) and cadmium (Cd) is an important research direction in the prevention and control of Cd pollution of wheat in recent years. In this study, a typical wheat field in North China was selected as the object to explore the control effect and application risk of Zn fertilizer on Cd pollution in a soil-wheat system through field experiments. The results showed that under the treatment of a low dosage of Zn, the Cd concentrations in wheat grains in Jiyuan City and Kaifeng City decreased by 33.4% and 25.3% compared with those in the control, respectively. By contrast, Cd concentrations in wheat grains treated with a high dosage of Zn increased by 22.4% and 34.2% compared with that of the low-dosage Zn treatment. After the application of Zn, the total amount and available Zn concentrations increased significantly, and Cd was partially activated in these two locations. Canonical correlation analysis (CCA) showed that when the Zn concentrations in the soils were less than 200 mg·kg-1, soil Zn was the main factor affecting Cd accumulation in the soil-wheat system, whereas when Zn concentrations in soils were greater than 200 mg·kg-1, the activation of soil Cd was the main factor affecting Cd accumulation in wheat grains. Regression analysis showed that when the soil Cd/Zn ratio decreased to 0.0089 (low dosage of Zn), Zn and Cd showed an antagonistic effect, whereas when the soil Cd/Zn ratio decreased to 0.0078 (high dosage of Zn), Zn and Cd showed a synergistic effect. According to the characteristics of regional Cd pollution, adjusting the amount of Zn fertilizer can improve the efficiency of pollution control and avoid aggravating the harm of Cd pollution.


Subject(s)
Cadmium , Soil Pollutants , Cadmium/analysis , Zinc , Triticum , Fertilizers/analysis , Soil Pollutants/analysis , Edible Grain/chemistry , Soil
5.
J Ethnopharmacol ; 299: 115546, 2022 Dec 05.
Article in English | MEDLINE | ID: mdl-35850313

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Salvia miltiorrhiza Bunge and Panax ginseng C. A. Meyer have special curative effect on cancer treatment. The optimizing component formula (OCF) extracted from those two herbs was in line with the anti-lung cancer treatment principle of activating blood and supplementing 'Qi'. However, the study on the mechanism of component formula has always been an insurmountable challenge. Nowadays, the application of network pharmacology and artificial intelligence (AI) in the field of TCM provides new ideas for the study of new targets and mechanisms of TCM, which promotes the modernization of TCM. AIM OF THE STUDY: This study aims to further explore the anti-lung cancer mechanism of OCF by using an integrated strategy of network pharmacology and AI technology. MATERIALS AND METHODS: Bioinformatic analysis was used to analyze the expression levels, prognosis and survival of DTL and PDCD4 in cancer patients. The binding strength of OCF and DTL was simulated by molecular docking, and the affinity between them was detected by Bio-layer interferometry. Network pharmacology was used to predict the active components, potential targets and pathways of OCF. The association between key targets and their corresponding components and DTL was analyzed by Ingenuity Pathway Analysis (IPA). MTT assay, colony formation assay, wound-healing assay and transwell assay were used to verify the inhibitory effects of OCF on lung cancer cells in vitro. qRT-PCR and Western blot assay were used to detect the effects of OCF on mRNA and protein expression of DTL, PDCD4 and key genes in MAPK/JNK pathways. RESULTS: Bioinformatics analysis showed that DTL was significantly up-regulated in lung cancer, which was associated with high malignancy rate, high metastasis rate and poor prognosis of primary tumor. PDCD4 was down-regulated in lung cancer, and associated with high metastasis rate and poor prognosis. The good affinity between OCF and DTL was predicted and verified by molecular docking and Bio-layer interferometry. Based on the network pharmacological databases, 40 active components and 220 corresponding targets of OCF were screened out. KEGG analysis showed that OCF component targets were mainly enriched in MAPK signaling pathway. IPA results showed the interrelationship between DTL, PDCD4, MAPK pathway genes and their corresponding OCF components. In addition, in vitro experiments demonstrated anti-lung cancer activity of OCF, as validated, via impairing cell viability and cell proliferation, as well as inhibiting migration and invasion abilities in lung cancer cells. qRT-PCR showed that OCF down-regulated the mRNA expression of DTL, MAP4K1, JNK, c-Jun and c-Myc, and up-regulated the mRNA expression of PDCD4 and P53 genes in A549 lung cancer cells. Western blot suggested that OCF suppressed the protein level of DTL and blocked the ubiquitination of PDCD4 in A549 lung cancer cells, and down-regulated the protein levels of MAP4K1, p-JNK and p-c-Jun while up-regulated the proteins expression level of P53. CONCLUSIONS: OCF might elicit an anti-lung cancer effect by blocking DTL-mediated PDCD4 ubiquitination and suppression of the MAPK/JNK pathway. Meanwhile, our work revealed that network pharmacology and AI technology strategy are cogent means of studying the active components and mechanism of TCM.


Subject(s)
Lung Neoplasms , MAP Kinase Signaling System , Apoptosis Regulatory Proteins/genetics , Apoptosis Regulatory Proteins/metabolism , Artificial Intelligence , Humans , Lung Neoplasms/drug therapy , Molecular Docking Simulation , Nuclear Proteins/metabolism , RNA, Messenger/metabolism , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism , Tumor Suppressor Protein p53/metabolism , Ubiquitination
6.
Oxid Med Cell Longev ; 2021: 6685282, 2021.
Article in English | MEDLINE | ID: mdl-33777320

ABSTRACT

Lung cancer has become the leading cause of cancer-related death worldwide. Oxidative stress plays important roles in the pathogenesis of lung cancer. Many natural products show antioxidative activities in cancer treatment. Zi Shen decoction (ZSD) is a classic prescription for the treatment of lung disease. However, its effect on lung cancer lacks evidence-based efficacy. In this study, we investigated the anticancer effects of ZSD on lung cancer in vivo and in vitro. Our results showed that oral administration of ZSD suppressed the Lewis lung cancer (LLC) growth in a subcutaneous allograft model and promoted necrosis and inflammatory cell infiltration in the tumor tissues. Furthermore, ZSD not only inhibited tumor cell proliferation and migration but also induced cell apoptosis in lung cancer cells. PI3K/AKT signaling is well characterized in response to oxidative stress. The bioinformatics analysis and western blot assays suggested that ZSD decreased the enzyme activity of PI3K and AKT in vivo and in vitro. We also found that the AKT/GSK-3ß/ß-catenin pathway medicated anticancer effect of ZSD in lung cancer cells. In conclusion, we demonstrate for the first time that ZSD possesses antitumor properties, highlighting its potential use as an alternative strategy or adjuvant treatment for lung cancer therapy.


Subject(s)
Carcinoma, Lewis Lung , Drugs, Chinese Herbal/pharmacology , Glycogen Synthase Kinase 3 beta/metabolism , Lung Neoplasms , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction/drug effects , beta Catenin/metabolism , Animals , Carcinoma, Lewis Lung/drug therapy , Carcinoma, Lewis Lung/metabolism , Carcinoma, Lewis Lung/pathology , Lung Neoplasms/drug therapy , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Male , Mice , Neoplasm Metastasis
7.
Pharmacol Res ; 160: 105086, 2020 10.
Article in English | MEDLINE | ID: mdl-32687951

ABSTRACT

Traditional Chinese medicine (TCM) plays a vital part in cancer treatment due to its unique superiority. Huoxue Yiqi Recipe-2 (HYR-2) was supposed to have therapeutic effect on lung cancer, which came from Ze Qi Decoction in one of the four great classics of TCM called "Synopsis of Prescriptions of the Golden Chamber". Network pharmacology demonstrated that the targets of active components from HYR-2 were significantly enriched in the signaling pathways, which were closely associated with non-small cell lung cancer (NSCLC) and programmed death ligand 1 (PD-L1). Then, data about NSCLC was downloaded from Gene Expression Omnibus database (GEO). The Cancer Genome Atlas (TCGA) and DisGeNET was analyzed by bioinformatics, and 214 biomarkers for NSCLC were obtained, containing 14 targets of active components from HYR-2 (which were significantly enriched in the PD-L1 related signaling pathway). In vivo and in vitro experiments showed that HYR and HYR-2 could inhibit the growth of lung cancer and down-regulate the expression of PD-L1, which might be related to the blocking effect of HYR-2 on the PI3K/Akt signaling pathway. Furthermore, HYR-2 promoted the transformation of M2 macrophages into M1 macrophages as well. It is deserved to be mentioned that the level of Akkermansia muciniphila was also significantly elevated by HYR-2, which was believed to enhance the therapeutic effect of PD-L1 antibodies. To sum up, HYR-2 might play an anti-lung cancer effect by down-regulating PD-L1 together with up-regulating Akkermansia muciniphila.


Subject(s)
B7-H1 Antigen/antagonists & inhibitors , Carcinoma, Non-Small-Cell Lung/drug therapy , Drugs, Chinese Herbal/pharmacology , Immune Checkpoint Inhibitors/pharmacology , Lung Neoplasms/drug therapy , Medicine, Chinese Traditional , A549 Cells , Akkermansia/drug effects , Akkermansia/growth & development , Animals , B7-H1 Antigen/genetics , B7-H1 Antigen/metabolism , Carcinoma, Lewis Lung/drug therapy , Carcinoma, Lewis Lung/genetics , Carcinoma, Lewis Lung/immunology , Carcinoma, Lewis Lung/metabolism , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/immunology , Carcinoma, Non-Small-Cell Lung/metabolism , Cell Proliferation/drug effects , Gene Regulatory Networks , Hep G2 Cells , Humans , Lung Neoplasms/genetics , Lung Neoplasms/immunology , Lung Neoplasms/metabolism , MCF-7 Cells , Macrophages/drug effects , Macrophages/metabolism , Male , Mice, Inbred C57BL , Phenotype , Protein Interaction Maps , Signal Transduction , Tumor Burden/drug effects
9.
Environ Sci Pollut Res Int ; 27(24): 30831-30843, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32474781

ABSTRACT

Permeable pavements, as additive structures that have a good capability for runoff and pollutant reduction, are extensively used for sustainable urban drainage techniques. However, the exact mechanisms of runoff retention and pollutant reduction of a permeable pavement system remain unclear and so, it has become an ongoing issue and motivation for hydrologists and design and structural engineers. In this research paper, a suite of four scale-based runoff plots representing permeable pavements were designed with different permeable surface types and gravel layer thickness treatments, and coupled with simulated rainfall experiments to analyze the impacts of structural factors of permeable pavements on runoff retentions and pollution reduction. The present results showed that the average time to runoff for permeable pavements under low-intensity rainfall scenarios was approximately 78.5 min, while this was shortened to only 51.5 min under high-intensity rainfall scenarios. In terms of the average runoff retention of permeable pavements tested under low- and high-intensity rainfall cases, the results recorded approximately 52.5% and 42.5%, respectively, but runoff retention performances were relatively greater for the case of smaller storms within the scale experiments. Importantly, there was no statistical significance for the time to runoff and runoff retention between the permeable bricks and porous concretes for the analyzed rainfall events. The thicker gravel layers significantly delayed runoff generation and increased runoff retention percentages. Runoff pollutant load reduction rates of total suspended solids (TSS), total nitrogen (TN), and total phosphorus (TP) were varied between permeable bricks and porous concretes. Runoff pollutants load reduction rates of TSS, TN, and TP were highly enhanced while the gravel layer thickness increased from 10 to 20 cm. Higher TSS, TN, and TP pollutant load removals were found from the lower intensity rainfalls. These findings could promote understanding of the hydrologic properties of permeable pavements and help design engineers in optimizing their design of permeable pavements for better runoff retention and pollution removal.


Subject(s)
Water Movements , Water Pollutants, Chemical/analysis , Environmental Monitoring , Phosphorus/analysis , Rain , Water Pollution
12.
Brain Res ; 1736: 146730, 2020 06 01.
Article in English | MEDLINE | ID: mdl-32081533

ABSTRACT

OBJECTIVES: To investigate the neuroprotective effect of Gingko biloba extract 761 (EGb761) in Alzheimer's disease (AD) models both in vivo and in vitro and the underlying molecular mechanism. METHODS: Cultured BV2 microglial cells were treated with Aß1-42 to establish an in vitro AD model. The in vivo rat AD model was established by injecting Aß1-42. Cells were pre-treated with EGb761, and the proliferation and necroptosis were examined by MTT or flow cytometry assays, respectively. In addition, the membrane potential and oxidative stress were measured. Cognitive function was evaluated by the Morris water maze, and the activation of the JNK signaling pathway was quantified by Western blotting. RESULTS: Cultured BV2 cells exhibited prominent cell death after Aß1-42 induction, and this cell death was alleviated by EGb761 pre-treatment. EGb761 was found to relieve oxidative stress and suppress the membrane potential and calcium overload. EGb761 treatment in AD model rats also improved cognitive function deficits. Both cultured microglial cells and the rat hippocampus exhibited activation of the JNK signaling pathway, and EGb761 relieved this activation in cells. CONCLUSION: Our results showed that EGb761 regulated cell proliferation, suppressed necroptosis and apoptosis, relieved mitochondrial damage, and ameliorated tissue damage to improve cognitive function in AD models. All of these effects may involve the suppression of the JNK signaling pathway.


Subject(s)
Alzheimer Disease/metabolism , Necroptosis/drug effects , Plant Extracts/pharmacology , Alzheimer Disease/drug therapy , Amyloid beta-Peptides/metabolism , Animals , Apoptosis/drug effects , Brain/metabolism , Cell Line , Cognition Disorders/drug therapy , Cognitive Dysfunction/metabolism , Disease Models, Animal , Ginkgo biloba , Hippocampus/metabolism , Humans , Male , Microglia , Mitochondria/metabolism , Mitochondrial Diseases/drug therapy , Mitochondrial Diseases/metabolism , Neurons/metabolism , Neuroprotective Agents/pharmacology , Oxidative Stress/drug effects , Peptide Fragments/metabolism , Plant Extracts/metabolism , Protein Serine-Threonine Kinases/metabolism , Protein Serine-Threonine Kinases/physiology , Rats , Rats, Wistar , Reactive Oxygen Species/metabolism , Receptor-Interacting Protein Serine-Threonine Kinases
13.
Theranostics ; 9(26): 8109-8126, 2019.
Article in English | MEDLINE | ID: mdl-31754384

ABSTRACT

Rationale: Ascorbate is an essential micronutrient known for redox functions at normal physiologic concentrations. In recent decades, pharmacological ascorbate has been found to selectively kill tumour cells. However, the dosing frequency of pharmacologic ascorbate in humans has not yet been defined. Methods: We determined that among five hepatic cell lines, Huh-7 cells were the most sensitive to ascorbate. The effects of high-dose ascorbate on hepatoma were therefore assessed using Huh-7 cells and xenograft tumour mouse model. Results: In Huh-7 cells, ascorbate induced a significant increase in the percentage of cells in the G0/G1 phase, apoptosis and intracellular levels of ROS. High doses of ascorbate (4.0 pmol cell-1), but not low doses of ascorbate (1.0 pmol cell-1), also served as a pro-drug that killed hepatoma cells by altering mitochondrial respiration. Furthermore, in a Huh-7 cell xenograft tumour mouse model, intraperitoneal injection of ascorbate (4.0 g/kg/3 days) but not a lower dose of ascorbate (2.0 g/kg/3 days) significantly inhibited tumour growth. Gene array analysis of HCC tumour tissue from xenograft mice given IP ascorbate (4.0 g/kg/3 days) identified changes in the transcript levels of 192 genes/ncRNAs involved in insulin receptor signalling, metabolism and mitochondrial respiration. Consistent with the array data, gene expression levels of AGER, DGKK, ASB2, TCP10L2, Lnc-ALCAM-3, and Lnc-TGFBR2-1 were increased 2.05-11.35 fold in HCC tumour tissue samples from mice treated with high-dose ascorbate, and IHC staining analysis also verified that AGER/RAGE and DGKK proteins were up-regulated, which implied that AGER/RAGE and DGKK activation might be related to oxidative stress, leading to hepatoma cell death. Conclusions: Our studies identified multiple mechanisms are responsible for the anti-tumour activity of ascorbate and suggest high doses of ascorbate with less frequency will act as a novel therapeutic agent for liver cancer in vivo.


Subject(s)
Ascorbic Acid/pharmacology , Carcinoma, Hepatocellular/drug therapy , Cell Line, Tumor/drug effects , Animals , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Cell Death/drug effects , Cell Line , Cell Proliferation/drug effects , Disease Models, Animal , Gene Expression Regulation, Neoplastic/drug effects , Gene Expression Regulation, Neoplastic/genetics , Liver Neoplasms/drug therapy , Mice , Oxidative Stress/drug effects , Oxidative Stress/genetics , Reactive Oxygen Species , Signal Transduction/drug effects , Signal Transduction/genetics
14.
J Agric Food Chem ; 67(44): 12199-12207, 2019 Nov 06.
Article in English | MEDLINE | ID: mdl-31595753

ABSTRACT

Salvianolic acid A (Sal A) has a wide range of pharmacological activities. To date, there have been no systematic and detailed metabolite research data of Sal A after oral administration in vitro and in vivo. In this study, a rapid and systematic method based on ultrafast liquid chromatography-quadrupole-time-of-flight mass spectrometry was developed to detect metabolites of Sal A in vitro (human liver microsome, human intestinal microbiota, artificial gastric, and intestinal juice) and in vivo (urine, plasma, feces, and various organs collected after oral administration of Sal A to normal rats and pseudo-germ-free rats). A total of 26 metabolites of Sal A were characterized. These metabolites were formed through extensive metabolic reactions, such as hydroxylation, hydrogenation, and glucuronidation reactions. This study provides novel possibility for exploring the potential biological mechanism of Sal A, and aids the promotion of clinical application.


Subject(s)
Caffeic Acids/chemistry , Caffeic Acids/metabolism , Chromatography, High Pressure Liquid/methods , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/metabolism , Lactates/chemistry , Lactates/metabolism , Mass Spectrometry/methods , Salvia miltiorrhiza/chemistry , Adult , Animals , Female , Humans , Male , Metabolome , Microsomes, Liver/chemistry , Microsomes, Liver/metabolism , Rats , Rats, Sprague-Dawley , Young Adult
15.
Environ Pollut ; 255(Pt 1): 113184, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31541819

ABSTRACT

Assessing the ecological risk of combined pollution, especially from a holistic perspective with the consideration of the overarching functions of soil ecosystem, is crucial and beneficial to the improvement of ecological risk assessment (ERA) framework. In this study, four soils with similar physicochemical properties but contrasting heavy metals contamination levels were selected to explore changes in the integrated functional sensitivity (MSI), resistance (MRS) and resilience (MRL) of soil microbial communities subjected to herbicide siduron, based on which the ecological risk of the accumulation of siduron in the four studied soils were evaluated. The results suggested that the microbial biomass carbon, activity of denitrification enzyme and nitrogenase were indicative of MSI and MRS, and the same three parameters plus soil basal respiration were indicative of MRL. Significant dose-effect relationships between siduron residues in soils and MSI, MRS and MRL under combined pollution were observed. Heavy metal polluted soils showed higher sensitivity and lower resistance to the additional disturbance of herbicide siduron due to the lower microbial biomass, while the resilience of heavy metal polluted soils was much higher due to the pre-adaption to the chemical stresses. The quantifiable indicator microbial functional stability was incorporated in the framework of ERA and the results showed that the accumulation of siduron in the studied soils could exhibit potential harm to the integrated functional stability of soil microbial community. Thus, this work provides insights into the application of integrated function of soil microbial community into the framework of ERA.


Subject(s)
Herbicides/toxicity , Phenylurea Compounds/toxicity , Soil Microbiology , Soil Pollutants/toxicity , Soil/chemistry , Biomass , Ecosystem , Metals, Heavy/toxicity , Risk Assessment
16.
J Ethnopharmacol ; 232: 11-20, 2019 Mar 25.
Article in English | MEDLINE | ID: mdl-30529424

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Chinese medicine, supplementing Qi and strengthening body resistance are an important principle of anticancer treatment. Panax ginseng C.A.Mey. (ginseng) and Astragalus membranaceus Bunge (astragalus) are the representative herbs for this therapeutic principle. AIM OF THE STUDY: This study aims to explore the effect of the water extract of ginseng and astragalus (WEGA) on regulating macrophage polarization and mediating anticancer in the tumor microenvironment. MATERIALS AND METHODS: A549 cells were cultured in tumor-associated macrophage (TAM) supernatant with various concentrations of WEGA (0, 5, 10, 20 mg/mL). A549 cell proliferation was determined through methyl thiazole tetrazolium (MTT) assay and real-time cell analysis (RTCA), respectively. In vivo experiments were performed with a Lewis lung cancer (LLC) xenograft mouse model. Forty-eight mice were divided into six groups and treated with saline, WEGA, or cis-diamine dichloro platinum (DDP) with dosage of WEGA (0, 30, 60, 120 mg/kg body weight/day). The different groups were administered with drugs via oral or intraperitoneal injection once a day for 21 consecutive days. Tumor inhibition rate, spleen index, thymus index, cytokine, protein, and mRNA expression levels were detected in mice. RESULTS: In a co-culture system, WEGA remarkably inhibited A549 cell proliferation, promoted the expression of M1 macrophage markers and inhibited M2 TAMs markers. Therefore, WEGA affected the biological behavior of cancer cells by regulating the expression of some markers relevant to macrophage polarization. In addition, the group of WEGA and DDP chemotherapy effectively inhibited the transplanted tumor growth in mice and improved weight loss and immunosuppressive with the cisplatin inducing. CONCLUSIONS: This study provides mechanistic insights into the anticancer effect of WEGA through the regulation of macrophage polarization and highlights that WEGA could be a novel option for integrative cancer therapies.


Subject(s)
Antineoplastic Agents , Astragalus Plant , Carcinoma, Lewis Lung , Lung Neoplasms , Macrophages/drug effects , Panax , Plant Extracts , Animals , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Carcinoma, Lewis Lung/drug therapy , Carcinoma, Lewis Lung/immunology , Carcinoma, Lewis Lung/pathology , Cell Line, Tumor , Cell Polarity/drug effects , Cisplatin/therapeutic use , Cytokines/immunology , Drug Synergism , Female , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/immunology , Lung Neoplasms/pathology , Macrophages/physiology , Mice, Inbred C57BL , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Solvents/chemistry , Tumor Microenvironment/drug effects , Tumor Microenvironment/physiology , Water/chemistry
17.
Nucleic Acids Res ; 47(D1): D1118-D1127, 2019 01 08.
Article in English | MEDLINE | ID: mdl-30357356

ABSTRACT

The beneficial effects of functionally useful plants (e.g. medicinal and food plants) arise from the multi-target activities of multiple ingredients of these plants. The knowledge of the collective molecular activities of these plants facilitates mechanistic studies and expanded applications. A number of databases provide information about the effects and targets of various plants and ingredients. More comprehensive information is needed for broader classes of plants and for the landscapes of individual plant's multiple targets, collective activities and regulated biological pathways, processes and diseases. We therefore developed a new database, Collective Molecular Activities of Useful Plants (CMAUP), to provide the collective landscapes of multiple targets (ChEMBL target classes) and activity levels (in 2D target-ingredient heatmap), and regulated gene ontologies (GO categories), biological pathways (KEGG categories) and diseases (ICD blocks) for 5645 plants (2567 medicinal, 170 food, 1567 edible, 3 agricultural and 119 garden plants) collected from or traditionally used in 153 countries and regions. These landscapes were derived from 47 645 plant ingredients active against 646 targets in 234 KEGG pathways associated with 2473 gene ontologies and 656 diseases. CMAUP (http://bidd2.nus.edu.sg/CMAUP/) is freely accessible and searchable by keywords, plant usage classes, species families, targets, KEGG pathways, gene ontologies, diseases (ICD code) and geographical locations.


Subject(s)
Computational Biology/methods , Crops, Agricultural/chemistry , Databases, Factual , Plant Preparations/therapeutic use , Plants, Medicinal/chemistry , Computational Biology/statistics & numerical data , Drug Discovery/methods , Information Storage and Retrieval/methods , Internet , Molecular Targeted Therapy/methods , Signal Transduction/drug effects , User-Computer Interface
18.
Oncotarget ; 8(60): 101599-101613, 2017 Nov 24.
Article in English | MEDLINE | ID: mdl-29254189

ABSTRACT

Lung cancer still remains the leading cause of cancer-related death worldwide. It is an urgent need for development of novel therapeutic agents to improve current treatment of this disease. Here we investigate whether the effective component formula of traditional Chinese Medicine could serve as new potential therapeutic drugs to treat lung cancer. We optimize the most effective component formula of Salvia miltiorrhiza and Panax Ginseng (FMG), which is composed of Salvianolic acid A, 20(S)-Ginsenoside and Ginseng polysaccharide. We discovered that FMG selectively inhibited lung cancer cell proliferation and induced apoptosis but had no any cytotoxic effects on normal lung epithelial BEAS-2B cells. Moreover, FMG inhibited lung cancer cell migration and invasion. Mechanistically, we found that FMG significantly promoted p-PTEN expression and subsequently inhibited PI3K/AKT signaling pathway. The phosphatase activity of PTEN protein was increased after FMG bound to PTEN protein, indicating that PTEN is one of the FMG targeted proteins. In addition, FMG regulated expression of some marker proteins relevant to cell apoptosis, migration and invasion. Collectively, these results provide mechanistic insight into the anti-NSCLC of FMG by enhancing the phosphatase activity of PTEN, and suggest that FMG could be as a potential option for lung cancer treatment.

19.
Environ Monit Assess ; 189(12): 602, 2017 Nov 03.
Article in English | MEDLINE | ID: mdl-29101549

ABSTRACT

Considerable growth in the economy and population of the Dongting Lake watershed in Southern China has increased phosphorus loading to the lake and resulted in a growing risk of lake eutrophication. This study aimed to reveal the spatial pattern and sources of phosphorus export and loading from the watershed. We applied an export coefficient model and the Dillon-Rigler model to quantify contributions of different sub-watersheds and sources to the total phosphorus (TP) export and loading in 2010. Together, the upper and lower reaches of the Xiang River watershed and the Dongting Lake Area contributed 60.9% of the TP exported from the entire watershed. Livestock husbandry appeared to be the largest anthropogenic source of TP, contributing more than 50% of the TP exported from each secondary sub-watersheds. The actual TP loading to the lake in 2010 was 62.9% more than the permissible annual TP loading for compliance with the Class III water quality standard for lakes. Three primary sub-watersheds-the Dongting Lake Area, the Xiang River, and the Yuan River watersheds-contributed 91.2% of the total TP loading. As the largest contributor among all sources, livestock husbandry contributed nearly 50% of the TP loading from the Dongting Lake Area and more than 60% from each of the other primary sub-watersheds. This study provides a methodology to identify the key sources and locations of TP export and loading in large lake watersheds. The study can provide a reference for the decision-making for controlling P pollution in the Dongting Lake watershed.


Subject(s)
Environmental Monitoring , Phosphorus/analysis , Water Pollutants, Chemical/analysis , Water Quality , China , Eutrophication , Lakes/chemistry , Models, Theoretical , Rivers/chemistry
20.
Environ Sci Pollut Res Int ; 24(34): 26706-26723, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28956238

ABSTRACT

Socioeconomic development in lake watersheds is closely related with lake nutrient pollution. As the second largest freshwater lake in China, the Dongting Lake has been experiencing an increase in nutrient loading and a growing risk of eutrophication. This study aimed to reveal the likely impacts of the socioeconomic development of the Dongting Lake watershed on the phosphorous pollution in the lake. We estimated the contributions from different sources and sub-watersheds to the total phosphorous (TP) export and loading from the Dongting Lake watershed under two most likely socioeconomic development scenarios. Moreover, we predicted the likely permissible and actual TP loadings to the Dongting Lake. Under both two scenarios, three secondary sub-watersheds-the upper and lower reaches of the Xiang River watershed and the Dongting Lake Area-are expected to dominate the contribution to the TP export from the Dongting Lake watershed in 2020. Three primary sub-watersheds-the Dongting Lake Area, the Xiang River, and the Yuan River watersheds-are predicted to be the major contributors to the TP loading from the entire watershed. The two scenarios are expected to have a slight difference in TP export and lake TP loading. Livestock husbandry is expected to be the predominant anthropogenic TP source in each of the sub-watersheds under both scenarios. Compared to 2010, permissible TP loading is not expected to increase but actual TP loading is predicted to grow significantly in 2020. Our study provides methodologies to identify the key sources and regions of lake nutrient loading from watersheds with complex socioeconomic context, and to reveal the potential influences of socioeconomic development on nutrient pollution in lake watersheds.


Subject(s)
Economic Development , Environmental Monitoring/methods , Lakes/chemistry , Phosphorus/analysis , Water Pollutants, Chemical/analysis , China , Environmental Monitoring/economics , Eutrophication , Rivers/chemistry , Socioeconomic Factors
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