Ginsenoside Rg5 inhibits glioblastoma by activating ferroptosis via NR3C1/HSPB1/NCOA4.

BACKGROUND: The utilization of Chinese medicine as an adjunctive therapy for cancer has recently gained significant attention. Ferroptosis, a newly regulated cell death process depending on the ferrous ions, has been proved to be participated in glioma stem cells inactivation. PURPOSE: We aim to study whether ginsenoside Rg5 exerted inhibitory effects on crucial aspects of glioma stem cells, including cell viability, tumor initiation, invasion, self-renewal ability, neurosphere formation, and stemness. METHODS: Through comprehensive sequencing analysis, we identified a compelling association between ginsenoside Rg5 and the ferroptosis pathway, which was further validated through subsequent experiments demonstrating its ability to activate this pathway. RESULTS: To elucidate the precise molecular targets affected by ginsenoside Rg5 in gliomas, we conducted an intersection analysis between differentially expressed genes obtained from sequencing and a database-predicted list of transcription factors and potential targets of ginsenoside Rg5. This rigorous approach led us to unequivocally confirm NR3C1 (Nuclear Receptor Subfamily 3 Group C Member 1) as a direct target of ginsenoside Rg5, a finding consistently supported by subsequent experimental investigations. Moreover, we uncovered NR3C1's capacity to transcriptionally regulate ferroptosis -related genes HSPB1 and NCOA4. Strikingly, ginsenoside Rg5 induced notable alterations in the expression levels of both HSPB1 (Heat Shock Protein Family B Member 1) and NCOA4 (Nuclear Receptor Coactivator 4). Finally, our intracranial xenograft assays served to reaffirm the inhibitory effect of ginsenoside Rg5 on the malignant progression of glioblastoma. CONCLUSION: These collective findings strongly suggest that ginsenoside Rg5 hampers glioblastoma progression by activating ferroptosis through NR3C1, which subsequently modulates HSPB1 and NCOA4. Importantly, this novel therapeutic direction holds promise for advancing the treatment of glioblastoma.

Phosphorus deficiency-induced cell wall pectin demethylesterification enhances cadmium accumulation in roots of Salix caprea.

Regions affected by heavy metal contamination frequently encounter phosphorus (P) deficiency. Numerous studies highlight crucial role of P in facilitating cadmium (Cd) accumulation in woody plants. However, the regulatory mechanism by which P affects Cd accumulation in roots remains ambiguous. This study aims to investigate the effects of phosphorus (P) deficiency on Cd accumulation, Cd subcellular distribution, and cell wall components in the roots of Salix caprea under Cd stress. The results revealed that under P deficiency conditions, there was a 35.4% elevation in Cd content in roots, coupled with a 60.1% reduction in Cd content in shoots, compared to the P sufficiency conditions. Under deficient P conditions, the predominant response of roots to Cd exposure was the increased sequestration of Cd in root cell walls. The sequestration of Cd in root cell walls increased from 37.1% under sufficient P conditions to 66.7% under P deficiency, with pectin identified as the primary Cd binding site under both P conditions. Among cell wall components, P deficiency led to a significant 31.7% increase in Cd content within pectin compared to P sufficiency conditions, but did not change the pectin content. Notably, P deficiency significantly increased pectin methylesterase (PME) activity by regulating the expression of PME and PMEI genes, leading to a 10.4% reduction in the degree of pectin methylesterification. This may elucidate the absence of significant changes in pectin content under P deficiency conditions and the concurrent increase in Cd accumulation in pectin. Fourier transform infrared spectroscopy (FTIR) results indicated an increase in carboxyl groups in the root cell walls under P deficiency compared to sufficient P treatment. The results provide deep insights into the mechanisms of higher Cd accumulation in root mediated by P deficiency.

Chitosan-coated soybean protein isolate/lecithin nanoparticles for enhancing the stability and bioaccessibility of phytosterol.

BACKGROUND: Phytosterols (PS) have various beneficial effects on human health, especially the property of reducing blood cholesterol. However, the low solubility and bioaccessibility of PS have greatly limited their application in functional food ingredients. RESULTS: To improve the bioaccessibility and stability of PS, chitosan-coated PS nanoparticles (CS-PNP) were successfully prepared by self-assembly. The properties of CS-PNP, including size, zeta potential, encapsulation efficiency (EE) and loading amount (LA) were characterised. The optimisation of CS concentration (0.4 mg mL-1) and pH (3.5) resulted in the formation of CS-PNP with an EE of over 90% and a particle size of 187.7 nm. Due to the special properties of CS chitosan, the interaction between CS and soybean protein isolate (SPI)/lecithin (SL) led to the formation of a soluble complex. CS-PNP exhibited good stability to temperature variations but was more sensitive to salt ions. During in vitro digestion, CS efficiently maintained the stability of nanoparticles against the hydrolysis of SPI by pepsin under acidic conditions. However, these nanoparticles tended to aggregate in a neutral intestinal environment. After 3 h of in vitro digestion, the bioaccessibility of PS increased from 18.2% of free PS to 63.5% of CS-PNP. CONCLUSION: Overall, these results highlight the potential of chitosan-coated nanoparticles as effective carriers for the oral administration of PS. This multilayer construction may serve as a promising for applications in food products as delivery vehicles for nutraceuticals. © 2024 Society of Chemical Industry.

Toxic metals and the risks of sludge from the treatment of wastewater from beryllium smelting.

The release of highly toxic beryllium in sludge (BCS) produced by physico-chemical treatment of beryllium-containing wastewater from Be smelting production has become a growing concern with the widespread use of Be in the defense industry. This work investigated the potential mobility of Be in BCS. The toxicity characteristic leaching procedure (TCLP) of BCS showed that the amount of leached Be was up to 202 mg L-1, which exceeded the regulated limit by nearly 10,000 times. The chemical fractionation analysis further revealed that the excessive amount of Be leached from BCS was contributed to the high content of acid-soluble fraction and reducible fraction of Be, which accounted for over 70% of the Be content. The results obtained from mineralogical automatic analyzer (MLA) showed that gypsum (23.23%) and epidote (19.55%) were the two major mineralogical phases of BCS. Both were small and loosely structured agglomerated particles with a D50 of 6.61 µm and 3.31 µm. ToF-SIMS results revealed that the Be distribution on the surface of BCS particles was relatively dispersed, with no aggregation or encapsulation. Be co-precipitated with gypsum and chlorite in the form of unstable Be(OH)2, which attached to the surface of these small particles. The unstable state of Be and the small size, loose structure and high liberation of the host material phases are the main reasons for the high leaching mobility of Be. The results of the risk assessment indicated that BCS posed an extremely high potential ecological risk, with Be being the most significant contributor.

Boosting Simultaneous Uranium Decorporation and Reactive Oxygen Species Scavenging Efficiency by Lacunary Polyoxometalates.

The chemical toxicity and the oxidative stress induced by the internal exposure of uranium is responsible for the long-term adverse effect of in vivo contamination of uranium. An agent with simultaneous removal capability of uranium and excess reactive oxygen species (ROS) is highly desired. Herein, the lacunary Keggin-type polyoxometalate (POM) is demonstrated to selectively bind with uranyl ions in the presence of excess essential divalent ions and exhibits a compelling ROS scavenging efficiency of 78.8%. In vivo uranium decorporation assays illustrate the uranium sequestration efficiencies of 74.0%, 49.4%, and 37.1% from kidneys by prophylactic, prompt, and delayed administration of lacunary POM solution, respectively. The superior ROS quenching and uranium removal performance in comparison with all reported bifunctional agents endow lacunary polyoxometalates as novel agents to effectively protect people from injuries caused by the internal exposure of actinides.

Pyrolysis kinetics and environmental risks of oil-based drill cuttings at China's largest shale gas exploitation site.

Chongqing Fuling shale gas field, the largest shale gas exploration site in China, produces a large amount of oil-based drill cuttings (OBDC) every year, which is a hazardous waste. Traditional treatment methods such as solidification/stabilization did not recycle the valuable components such as petroleum hydrocarbons. Pyrolysis is proven to be an efficient method that can recover those components. This study firstly investigated the pyrolysis kinetics by two different methods on the basis of detailed material characterization, and then taking the workers and the surrounding ecological environment as the analysis object, the human health risk assessment (HHRA) and ecological risk assessment were evaluated respectively before and after pyrolysis. The results showed that the pyrolysis of OBDC was divided into three stages, and the cracking of light hydrocarbons stage was the key control step for pyrolysis process. The activation energy E increased gradually during the pyrolysis progress. The HHRA results showed that pyrolysis could greatly reduce the non-carcinogenic risk, carcinogenic risk and ecological risk by 59.6 %, 62.8 % and 75 % respectively. However, the carcinogenic risk after pyrolysis was still higher than the critical value 10-6.

The progress and prospect of natural components in rhubarb (Rheum ribes L.) in the treatment of renal fibrosis.

Background: Renal fibrosis is a key pathological change that occurs in the progression of almost all chronic kidney diseases . CKD has the characteristics of high morbidity and mortality. Its prevalence is increasing each year on a global scale, which seriously affects people's health and quality of life. Natural products have been used for new drug development and disease treatment for many years. The abundant natural products in R. ribes L. can intervene in the process of renal fibrosis in different ways and have considerable therapeutic prospects. Purpose: The etiology and pathology of renal fibrosis were analyzed, and the different ways in which the natural components of R. ribes L. can intervene and provide curative effects on the process of renal fibrosis were summarized. Methods: Electronic databases, such as PubMed, Life Science, MEDLINE, and Web of Science, were searched using the keywords 'R. ribes L.', 'kidney fibrosis', 'emodin' and 'rhein', and the various ways in which the natural ingredients protect against renal fibrosis were collected and sorted out. Results: We analyzed several factors that play a leading role in the pathogenesis of renal fibrosis, such as the mechanism of the TGF-ß/Smad and Wnt/ß-catenin signaling pathways. Additionally, we reviewed the progress of the treatment of renal fibrosis with natural components in R. ribes L. and the intervention mechanism of the crucial therapeutic targets. Conclusion: The natural components of R. ribes L. have a wide range of intervention effects on renal fibrosis targets, which provides new ideas for the development of new anti-kidney fibrosis drugs.

[Re-discussion on "Fenglong (ST 40) for phlegm"].

After reading the article, Tracing Origin and Development of "Fenglong (ST 40) for Phlegm": Examination and Verification published in Chinese Acupuncture & Moxibustion, the authors collected the original evidences also for the effect of Fenglong (ST 40) on phlegm disorders by tracing from 9 ancient books of acupuncture and moxibustion, explored the standardized expressions of its indications and analyzed the changes of its indications. In that article, it was viewed that the effect of Fenglong (ST 40) started to be generalized in treatment of phlegm disorders since the Ming Dynasty. On contrary, we believes that Fenglong (ST 40) works on strengthening the spleen and resolving dampness for the disorders caused by the broad meaning of "phlegm/damp". Based on it, since the Ming Dynasty, the effect of Fenglong (ST 40) is extended specifically for the disorders caused by the visible sputum from the lung, the narrowing mean of "phlegm". Hence, if "Fenglong (ST 40) for phlegm" is considered as an academic point of view, it needs an adequate evidences to expound and prove.

The dominant microbial metabolic pathway of the petroleum hydrocarbons in the soil of shale gas field: Carbon fixation instead of CO2 emissions.

In shale gas mining areas, indigenous microorganisms degrade organic pollutants such as petroleum hydrocarbons into carbon dioxide (CO2) and water (H2O) through aerobic metabolism. A large quantity of CO2 emissions will exacerbate the "Greenhouse effect". Based on the clean sieved soil and oil-based drilling fluid in the shale gas mining area, this experiment set three concentration gradients (3523 ± 159 mg/kg, 8715 ± 820 mg/kg and 22,031 ± 1533 mg/kg) to treat the soil, and each group was disposed for the same amount of time (63 days). By analyzing the dynamic changes of microbial diversity and the abundance of key functional genes for carbon fixation, the impact of petroleum hydrocarbons on carbon fixation potential was discovered, and the natural attenuation law of petroleum hydrocarbons in contaminated soil was explored. It provided the scientific research basis of ecology for the carbon cycle, carbon allocation, and carbon fixation in microbial remediation of petroleum hydrocarbon contaminated soil. The results obtained indicated the following: i) The removal rate of petroleum hydrocarbons under high-concentration pollution (45.33 ± 3.90%) was significantly lower than low and medium-concentration pollution. The TPH concentration removal rate of each group was the largest in the early stage of culture (1-5d), and there was no significant correlation between the TPH content and the community composition (R2 = 0.0736, P > 0.05). ii) Composition and function of Carbon Fixation associated microbiota were assessed by 16S rRNA sequencing and PICRUSt (phylogenetic investigation of communities by reconstruction of unobserved states) analysis. The main carbon fixation pathway in this study is the reductive citric acid cycle, because there was no shortage of enzymes that can affect subsequent reactions.

Dual enzyme-mimic nanozyme based on single-atom construction strategy for photothermal-augmented nanocatalytic therapy in the second near-infrared biowindow.

Nanozyme-based catalytic therapy, an emerging therapeutic pattern, has significantly incorporated in the advancement of tumor therapy by generating lethal reactive oxygen species. Nevertheless, most of the nanozymes have mono catalytic performances with H2O2 in the tumor microenvironment (TME), which lowers their therapeutic efficiency. Herein, we design a newly-developed single-atom Fe dispersed N-doped mesoporous carbon nanospheres (SAFe-NMCNs) nanozyme with high H2O2 affinity for photothermal-augmented nanocatalytic therapy. The SAFe-NMCNs nanozyme possesses dual enzyme-mimic catalytic activity which not only acts as a catalase-mimic role to achieve ultrasonic imaging in tumor site by O2 generation, but also exhibits the superior peroxidase-mimic catalytic performance to generate •OH for nanocatalytic therapy. Besides, the SAFe-NMCNs nanozyme with strong optical absorption in the second near-infrared (NIR-II) region shows excellent photothermal conversion performance. The peroxidase-mimic catalytic process of SAFe-NMCNs nanozyme is realized using density functional theory (DFT). Both in vitro and in vivo results indicate that the SAFe-NMCNs nanozyme can efficiently suppress tumor cells growth by a synergistic therapy effect with photothermal-augmented nanocatalytic therapy. The work developed a single-atom-coordinated nanozyme with dual-enzyme catalytic performance and achieve hyperthermia-augmented nanocatalytic therapy effect, can open a window for potential biological applications.

Effects of phloridzin on blood glucose and key enzyme G-6-Pase of gluconeogenesis in mice.

The effects of phloridzin (PHL), main component of Malus hupehensis (MH) tea leaves, on blood glucose (BG) and glucose-6-phosphatase (G-6-Pase) were investigated to provide a basis for finding a scheme of stabilizing BG. Glucose uptake of insulin resistant HepG2 cells was measured by glucose oxidase method. Glucose tolerance, fasting BG (FBG) and postprandial BG (PBG) were determined by BG test strips. The expression of G-6-Pase was detected by Western blot. The results showed that glucose uptake was enhanced and the expression of G-6-Pase was inhibited by PHL in insulin resistant HepG2 cells. Glucose tolerance was enhanced, FBG level was increased and PBG level was decreased by PHL in mice. The expression of G-6-Pase in the liver was enhanced under fasting state, and was inhibited by the low and medium dose under postprandial state. It indicated that PHL has a positive effect on stabilizing BG in mice, which is related to bidirectional regulation of G-6-Pase activity. PRACTICAL APPLICATIONS: Malus hupehensis, edible and medicinal plant, which has been proved by long-term application and experiments that it has a good effect on stabilizing blood glucose, preventing diabetes and adjuvant treatment. Its effect is closely related to its main component PHL. Thus, MH can be used as a dietary regulating drink for daily life to maintain blood glucose. Its main ingredient is PHL, which can be developed as a candidate drug for diabetes treatment.

MoO3-x nanosheets-based platform for single NIR laser induced efficient PDT/PTT of cancer.

Traditional combination therapy of photodynamic therapy (PDT) and photothermal therapy (PTT) is limited in the field of clinical cancer therapy due to activation by light with separate wavelengths, insufficient O2 supply, antioxidant ability of glutathione (GSH) in tumor cell, and low penetration depth of light. Here, a multifunctional nanoplatform composed of MoO3-x nanosheets, Ag nanocubes, and MnO2 nanoparticles was developed to overcome these drawbacks. For this nanoplatform, hyperthermia and reactive oxygen species (ROS) were simultaneously generated under single 808 nm near-infrared (NIR) light irradiation. Once this nanoplatform accumulated in the tumor region, GSH was depleted by MnO2 and intracellular H2O2 was catalyzed by MnO2 to produce O2 to relieve hypoxia. Ultrasound (US) imaging confirmed in-situ O2 generation. Magnetic resonance (MR) imaging, photoacoustic (PA) imaging, and fluorescence imaging were used to monitor in vivo biodistribution of nanomaterials. This provides a paradigm to rationally design a single NIR laser induced multimodal imaging-guided efficient PDT/PTT cancer strategy.

The Herbal Constituents in An-Gong-Niu-Huang Wan (AGNH) Protect against Cinnabar- and Realgar-Induced Hepatorenal Toxicity and Accumulations of Mercury and Arsenic in Mice.

An-Gong-Niu-Huang Wan (AGNH) has been a well-known cinnabar- and realgar-containing compound recipe for cerebral diseases. Unfortunately, its clinical practice is often restrained by the specific hepatorenal toxicity of cinnabar and realgar (C + R). In previous research studies, we have found that the antioxidative and anti-inflammatory effects of its herbal constituents could mitigate the risks from the toxicity. The underlying detoxification mechanisms are still unsolved. The present study investigated the protective effects of AGNH's herbal constituents on hepatorenal injury induced by C + R. For the mice treated with C + R, the increased expression levels of sensitive biomarkers of metal exposure and hepatorenal toxicity, including metallothionein (MT) in both hepatorenal tissues and kidney induced molecule-1 (KIM-1) in the kidney, were simultaneously reduced when C + R coadministered with other herbal medicines. In addition, the contents of trivalent As (AsIII), pentavalent As (Asv), and mercury (Hg) in hepatorenal tissues of mice were also significantly reduced benefiting from the herbal constituents in AGNH. Further mechanism studies showed that the herbal constituents in AGNH could downregulate the expressions of uptake transporters (AQP9 and OAT1) and upregulate the expressions of efflux transporters (P-gp, MRP2, and MRP4) in mice intoxicated by C + R. Our results suggested that AGNH's herbal constituents protect the body against C + R-induced hepatorenal toxicity and accumulations of Hg and As, which could be associated with the reestablishment of heavy metal homeostasis and the detoxification system.

Danggui Buxue Decoction in the Treatment of Metastatic Colon Cancer: Network Pharmacology Analysis and Experimental Validation.

PURPOSE: This study aimed to reveal Danggui Buxue Decoction (DBD) candidate targets and mechanisms in the treatment of metastatic colon cancer (MCC), using network pharmacology-based analyses and experimental validation. METHODS: Traditional Chinese Medicine Systems Pharmacology (TCMSP) database query and text mining were used to screen active compounds in DBD, and the Swiss target prediction platform was applied to predict compound-related target proteins. Targets likely associated with MCC were determined using GeneCards and OMIM databases. Targets common to DBD and MCC were obtained from the Venn platform; subsequently, Cytoscape was used to construct drug-compound-target-disease and protein-protein interaction networks. The hub gene was determined by R, while GO and KEGG enrichment analyses were performed on common targets to elucidate biological processes and signaling pathways involved in DBD against MCC. Finally, the metastatic colon cancer mouse model was used to detect the levels of expression of protein Bax, Bcl2, Caspase3, and Cleaved caspase3 by Western blot. RESULTS: A total of 28 active compounds and 61 common targets were predicted. The main compounds were quercetin, hederagenin, jaranol, methylnissolin, formononetin, calycosin, kaempferol, 3.9-di-O-methylnissolin, 24-propylcholesterol, and 7-O-methylisomucronulatol, present in Astragalus membranaceus (Huangqi, HQ). In addition, beta-sitosterol, ferulic acid, and stigmasterol, present in Angelica sinensis (Danggui, DG), were detected. JUN, PTSG2, EGFR, ESR1and, CASP3 genes were the top 5 hub genes in the PPI network. GO and KEGG enrichment analyses indicated that apoptosis played a major role in the biological processes and signaling pathways involved. Moreover, the in vivo experiment revealed that DBD inhibited MCC by up-regulating the expression of Bax, Caspase3, and Cleaved caspase3, and by down-regulating the expression of Bcl2. CONCLUSION: This study revealed candidate DBD targets and mechanisms in the treatment of MCC, using network pharmacology-based analyses and experimental validation. The present findings provide a reference for tumor treatment during the perioperative period.

A chromosome-scale genome assembly of a diploid alfalfa, the progenitor of autotetraploid alfalfa.

Alfalfa (Medicago sativa L.) is one of the most important and widely cultivated forage crops. It is commonly used as a vegetable and medicinal herb because of its excellent nutritional quality and significant economic value. Based on Illumina, Nanopore and Hi-C data, we assembled a chromosome-scale assembly of Medicago sativa spp. caerulea (voucher PI464715), the direct diploid progenitor of autotetraploid alfalfa. The assembled genome comprises 793.2 Mb of genomic sequence and 47,202 annotated protein-coding genes. The contig N50 length is 3.86 Mb. This genome is almost twofold larger and contains more annotated protein-coding genes than that of its close relative, Medicago truncatula (420 Mb and 44,623 genes). The more expanded gene families compared with those in M. truncatula and the expansion of repetitive elements rather than whole-genome duplication (i.e., the two species share the ancestral Papilionoideae whole-genome duplication event) may have contributed to the large genome size of M. sativa spp. caerulea. Comparative and evolutionary analyses revealed that M. sativa spp. caerulea diverged from M. truncatula ~5.2 million years ago, and the chromosomal fissions and fusions detected between the two genomes occurred during the divergence of the two species. In addition, we identified 489 resistance (R) genes and 82 and 85 candidate genes involved in the lignin and cellulose biosynthesis pathways, respectively. The near-complete and accurate diploid alfalfa reference genome obtained herein serves as an important complement to the recently assembled autotetraploid alfalfa genome and will provide valuable genomic resources for investigating the genomic architecture of autotetraploid alfalfa as well as for improving breeding strategies in alfalfa.

Xiaoyaosan, a traditional Chinese medicine, inhibits the chronic restraint stress-induced liver metastasis of colon cancer in vivo.

CONTEXT: Xiaoyaosan (XYS), a traditional Chinese medicine (TCM), has been widely used to relieve a variety of disorders caused by depression. OBJECTIVE: This study evaluates the effect of XYS against tumour metastasis in a chronic restraint stress mouse model. METHODS AND MATERIALS: Forty C57BL/6J mice were randomly divided into four groups, including blank-control (BC), blank-stress (BS), XYS-control (XC) and XYS-stress (XS). BS and XS groups were exposed to immobilization stress for 2 h per day for 28 days commencing seven days before tumour cell injection. XC and XS groups were given a gavage of XYS (1516.67 mg/kg) before chronic immobilization stress. Mice were injected with HT-29 colon cancer cells in the spleen to produce liver metastasis. After 28 days of injecting with HT-29 cells, flow cytometry, western blot, PCR and immunohistochemical staining were performed to uncover the role of chronic restraint stress and XYS in the liver metastasis of colon cancer. RESULTS: Metastatic liver weight of mice in XS group (3.33 ± 0.18 g) was significantly lower than BS group (4.01 ± 0.27 g). Chronic restraint stress significantly increased CD11b+F4/80+ and CD11b+GrloLy6Chi cell infiltration. XYS treatment significantly decreased the CD11b+F4/80+ tumour-associated macrophage (TAM) population and CD11b+GrloLy6Chi myeloid-derived suppressor cell (MDSC). TGF-ß, IL-6, MMP-9 and VEGF in spleen tumours significantly decreased in XYS group. XYS also reduced VEGF and CD31 in hepatic metastatic tissue, which were elevated by chronic restraint stress. CONCLUSIONS: XYS may successfully inhibit chronic-stress-induced liver metastasis. Results suggest that XYS may have therapeutic value for colorectal cancer treatment.

[Chemical composition analysis of Eucalyptus essential oil and allelopathic effects of α-terpineol]. / æ¡‰æ ‘æ²¹åŒ–å­¦æˆåˆ†åˆ†æžåŠα-松油醇的化感作用.

We extracted Eucalyptus essential oil by steam distillation and analyzed its chemical components by GC-MS. The inhibitory effects of α-terpineol, a component in Eucalyptus essential oil, were tested in Petri dishes on the germination and growth of Amaranthus retroflexus. The allelopathic effects of α-terpineol on A. retroflexus were examined with a pot experiment by measuring germination rate and biomass. The yield of essential oil was 0.04%. Ninety-two chemical components were detected from the essential oil. In Petri dish experiment, the germination inhibitory effect under 5 µL and 7.5 µL of α-terpineol per dish reached 100%. In pot experiment, germination, aboveground fresh and dry weights of A. retroflexus were significantly affected by α-terpineol. At the concentration of 1.6 µL·cm-3, the inhibition effect was strongest, with the allelopathic response index being -0.51 for germination, -0.62 for aboveground fresh weight, and -0.44 for aboveground dry weight, and the inhibition ratio being 51%, 62% and 44%, respectively.

Effect of mixed solutions of heavy metal eluents on soil fertility and microorganisms.

This study analyzed the effect of heavy metal eluents (0.3 mol/L C6H8O7, 5 × 10-4 mol/L EDTA, and 0.01 mol/L Na2S2O3) on the content of organic matter, hydrolytic nitrogen, available phosphorus and potassium, and species composition of bacteria and fungi in vegetable soils. The obtained results documented that the treatment of the soil, consisting of shaking the sample with a mixture of eluents, significantly increased the content of organic matter, hydrolytic nitrogen, and available phosphorus and potassium. The mixed solutions of eluents increase the maximum available P in the soil by 279.3%, and hydrolytic N by 30.7%. The eluents affected, to a certain extent, the dominant species of microorganisms in the soil, but did not increase species richness and evenness in all soil samples.

Toxicity assessment of artificially added zinc, selenium, and strontium in water.

The present research was to study the toxicology of artificially added Zn, Se and Sr in water. Specifically, we investigated the mortality and liver toxicity in zebrafish (Danio rerio), caused by different water concentrations of zinc sulfate (ZnSO4), sodium selenite (Na2SeO3), and strontium chloride hexahydrate (6H2O·SrCl2). Adult and embryo-larval zebrafish were used in the experiment. Analysis was performed of mortality, liver area and impermeability, delayed absorption area of the yolk sac, and liver tissue structure. The concentration change of sodium selenite exerted the most significant effect on the mortality of adult zebrafish, followed by that of strontium chloride hexahydrate, and zinc sulfate. Elevated strontium chloride hexahydrate concentration was associated with liver toxicity in zebrafish in the preliminary experiment. However, embryo-larval zebrafish were observed to die when the concentration of Zn2+ or Se4+ increased to a certain extent, without obvious liver toxicity. Our results indicated strontium chloride hexahydrate was hepatotoxic to embryo-larval zebrafish, which was manifested mainly as hepatomegaly and delayed absorption of the yolk sac. In addition, the artificially added strontium chloride hexahydrate destroyed liver tissue structure, resulting in hepatocyte enlargement, cell nucleus enlargement, blurred cytoplasmic boundaries, and formation of a vacuolar liver. These findings suggest the amount of strontium chloride hexahydrate added in soft drinks should be limited to certain levels.

Nagilactone E suppresses TGF-ß1-induced epithelial-mesenchymal transition, migration and invasion in non-small cell lung cancer cells.

BACKGROUND: Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer-related death around the world. Epithelial-mesenchymal transition (EMT) has been documented to increase motility and invasiveness of cancer cells, which promotes cancer metastasis. PURPOSE: This study aims to investigate the inhibitory effects and mechanisms of the dinorditerpenoids and norditerpenoids isolated from the seeds of Podocarpus nagi against transforming growth factor (TGF)-ß1-induced EMT. METHODS: A series of dinorditerpenoids and norditerpenoids were isolated from the seeds of P. nagi. Western blot and quantitative real-time PCR assays were performed to determine the expression levels of relative proteins and mRNA, along with immunofluorescence, Smad-binding element (SBE)-luciferase and chromatin immunoprecipitation (ChIP) assays for the mechanism study. Transwell assays were conducted to determine the effect of the compounds on cell migration and invasion. RESULTS: Nagilactone E (NLE) showed the superior inhibitory effect against TGF-ß1-induced EMT. NLE treatment dramatically inhibited TGF-ß1-induced expression of EMT markers in A549 cells. Mechanism study indicated that NLE markedly suppressed TGF-ß1-induced Smad2 and Smad3 activation and nuclear translocation. SBE-luciferase and ChIP assays showed that NLE inhibited the combining of Smad3 to SBE in the promoters of the cell signaling factors. NLE co-treatment attenuated TGF-ß1-induced up-regulation of the protein and mRNA levels of TGF-ß receptor TßRI. Furthermore, NLE inhibited TGF-ß1-stimulated cell migration and invasion, as well as up-regulation of the key signaling proteins related with migration and invasion. CONCLUSION: NLE inhibited TGF-ß/Smad signaling pathway, thereafter suppressed TGF-ß1-induced EMT, migration and invasion in NSCLC A549 cells.