Pharmacological Components and Mechanism Research on the Treatment of Myelosuppression after Chemotherapy with Danggui Jixueteng Decoction Based on Spectrum-Effect Relationships and Transcriptome Sequencing.

Danggui Jixueteng decoction (DJD) has been used to treat anemia for many years and has been shown to be effective. However, the mechanism of action and effective components are yet unknown. We want to search for pharmacodynamic components in DJD with therapeutic effects on myelosuppression after chemotherapy (MAC), utilizing a spectrum-effect connection study based on gray relational analysis and partial least-squares regression analysis. Transcriptome sequencing (RNA-Seq) was used to investigate the mechanism by which DJD treats MAC. In this study, fingerprints of different batches of DJD (S1-S10) were established by ultraperformance liquid chromatography-mass spectrometry (UPLC-MS), after which the resulting shared peaks were screened and identified. A total of 21 common peaks were screened through the fingerprints of different batches of DJD, and the similarity of each profile was greater than 0.92. The 21 shared peaks were identified by comparison with the standard sample and searching on a MassLynx 4.1 workstation. The rat model of MAC was established by intraperitoneal injection of cyclophosphamide, and DJD treatment was carried out in parallel with the establishment of the model. White blood cell count, red blood cell count, platelet count, interleukin-3, hemoglobin concentration, granulocyte-macrophage colony-stimulating factor, and nucleated cell count were used as efficacy indicators. Pharmacodynamic results indicated that DJD could effectively improve the pharmacodynamic indices of MAC rats. The results of gray relational analysis demonstrated eight peaks with high correlation with efficacy, which were 2, 7, 10, 14, 15, 16, 18, and 21, and the partial least-squares regression analysis showed four peaks with variable importance in projection values greater than 1, which were 10, 12, 13, and 19. RNA-Seq was used to identify DEGs in rat bone marrow cells, Gene Ontology functional enrichment and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of DEGs were performed. The genes related to the effects of DJD on MAC were mainly involved in the phosphatidylinositol 3-kinase/serine-threonine kinase (PI3K-Akt) signaling pathway, the mitogen-activated protein kinase signaling pathway, actin cytoskeleton regulation, focal adhesion, and Rap1 signaling pathways. The results of the RNA-Seq study were confirmed by a qPCR experiment. The effective compounds of DJD against MAC include albiflorin, paeoniflorin, gallopaeoniflorin, salvianolic acid H/I, albiflorin R1, salvianolic acid B, salvianolic acid E, benzoylpaeoniflorin, and C12H18N5O4. The mechanism by which DJD prevents and treats MAC might involve the control of the PI3K-Akt signaling pathway.

Advances in the chemical constituents, pharmacological activity, and clinical application of Smilacis Glabrae Rhizoma: A review and predictive analysis of quality markers (Q-markers).

Smilacis Glabrae Rhizoma (SGR) is recognized in traditional Chinese medicine for its distinctive therapeutic properties and abundant supply. Its phytochemical profile is diverse, encompassing flavonoids, steroids, saccharides, phenolic glycosides, volatile constituents, organic acids, phenylpropanoids, stilbenoids, among others. Recent pharmacological investigations reveal that SGR possesses a broad spectrum of pharmacological effects with multifaceted clinical applications. This review collates the current knowledge on SGR's chemical composition, pharmacological activities, and its clinical utility. Utilizing network pharmacology and molecular docking approaches, this study provides a preliminary identification of potential quality markers (Q-Markers) within SGR. The findings suggest that compounds such as astilbin, isoengelitin, neoisoastilbin, neoastilbin, astragaloside, diosgenin, resveratrol, stigmasterol, ß-sitosterol, and quercetin in SGR are promising candidates for Q-Markers. While flavonoids are the most extensively studied, there is a pressing need to further explore the active monomeric compounds within SGR. The introduction of Q-Markers is instrumental in developing standardized quality metrics. Specifically, astilbin has been noted for its antitumor, antidiabetic, antihypertensive, anti-hyperuricemic, and hepatoprotective potential, warranting further research for therapeutic applications.

Danggui Jixueteng decoction for the treatment of myelosuppression after chemotherapy: A combined metabolomics and network pharmacology analysis.

Objective: This study aimed to explore the mechanism of the Danggui Jixueteng decoction (DJD) in treating Myelosuppression after chemotherapy (MAC) through network pharmacology and metabolomics. Methods: We obtained the chemical structures of DJD compounds from TCMSP and PubMed. SwissTargetPrediction, STITCH, CTD, GeneCards, and OMIM were utilized to acquire component targets and MAC-related targets. We identified the key compounds, core targets, main biological processes, and signaling pathways related to DJD by constructing and analyzing related networks. The main active compounds and key proteins of DJD in treating AA were confirmed by molecular docking. A MAC rat model was established through intraperitoneal injection of cyclophosphamide to confirm DJD's effect on the bone marrow hematopoietic system. Untargeted metabolomics analyzed serum metabolite differences between MAC rats and the control group, and before and after DJD treatment, to explore DJD's mechanism in treating MAC. Results: Of the 93 active compounds identified under screening conditions, 275 compound targets and 3113 MAC-related targets were obtained, including 95 intersecting targets; AKT1, STAT3, CASP3, and JUN were key proteins in MAC treatment. The phosphatidylinositol-3-kinase/RAC-alpha serine/threonine-protein kinase (PI3K/AKT) signaling pathway may play a crucial role in MAC treatment with DJD. Molecular docking results showed good docking effects of key protein AKT1 with luteolin, ß-sitosterol, kaempferol, and glycyrrhizal chalcone A. In vivo experiments indicated that, compared to the model group, in the DJD group, levels of WBCs, RBCs, HGB, and PLTs in peripheral blood cells, thymus index increased, spleen index decreased, serum IL-3, GM-CSF levels increased, and IL-6, TNF-α, and VEGF levels decreased (p < 0.01); the pathological morphology of femoral bone marrow improved. Eleven differential metabolites were identified as differential serum metabolites, mainly concentrated in phenylalanine, tyrosine, and tryptophan biosynthesis pathways, phenylalanine metabolism, and arachidonic acid metabolism. Conclusion: This study revealed that DJD's therapeutic effects are due to multiple ingredients, targets, and pathways. DJD may activate the PI3K/AKT signaling pathway, promote hematopoietic-related cytokine production, regulate related metabolic pathways, and effectively alleviate cyclophosphamide-induced myelosuppression after chemotherapy in rats.

Fractionation and Lability of Phosphorus Species in Cottonseed Meal-Derived Biochars as Influenced by Pyrolysis Temperature.

Defatted cottonseed meal (CSM), the residue of cottonseeds after oil extraction, is a major byproduct of the cotton industry. Converting CSM to biochar and utilizing the goods in agricultural and environmental applications may be a value-added, sustainable approach to recycling this byproduct. In this study, raw CSM was transformed into biochar via complete batch slow pyrolysis at 300, 350, 400, 450, 500, 550, and 600 °C. Thermochemical transformation of phosphorus (P) in CSM during pyrolysis was explored. Fractionation, lability, and potential bioavailability of total P (TP) in CSM-derived biochars were evaluated using sequential and batch chemical extraction techniques. The recovery of feed P in biochar was nearly 100% at ≤550 °C and was reduced to <88% at 600 °C. During pyrolysis, the organic P (OP) molecules predominant in CSM were transformed into inorganic P (IP) forms, first to polyphosphates and subsequently to orthophosphates as promoted by a higher pyrolysis temperature. Conversion to biochar greatly reduced the mobility, lability, and bioavailability of TP in CSM. The biochar TP consisted of 9.3-17.9% of readily labile (water-extractable) P, 10.3-24.1% of generally labile (sequentially NaHCO3-extractable) P, 0.5-2.8% of moderately labile (sequentially NaOH-extractable) P, 17.0-53.8% of low labile (sequentially HCl-extractable) P, and 17.8-47.5% of residual (unextractable) P. Mehlich-3 and 1 M HCl were effective batch extraction reagents for estimating the "readily to mid-term" available and the "overall" available P pools of CSM-derived biochars, respectively. The biochar generated at 450 °C exhibited the lowest proportions of readily labile P and residual P compounds, suggesting 450 °C as the optimal pyrolysis temperature to convert CSM to biochar with maximal P bioavailability and minimal runoff risk.

Synthesis, Characterization and Biological Evaluation of Magnolol and Honokiol Derivatives with 1,3,5-Triazine of Metformin Cyclization.

Herein, we sought to evaluate the contribution of the 1,3,5-triazine ring through the metformin cyclization unit to the biological activity of magnolol and honokiol-conjugates. One of the phenolic OH groups of magnolol or honokiol was replaced by a 1,3,5-triazine ring to further explore their synthesis and medicinal versatility. In this study, a robust procedure of three steps was adopted for the synthesis of magnolol and honokiol derivatives by alkylation of potassium carbonate with a 1,3,5-triazine ring. To our knowledge, this is the first report to connect one of the phenolic OH positions of magnolol or honokiol to a 1,3,5-triazine ring cyclized by metformin. The structural characterization of three new compounds was carried out via spectroscopic techniques, i.e., 13C NMR, 1H NMR, and HRMS. Surprisingly, these compounds showed no cytotoxicity against RAW 264.7 macrophages but significantly inhibited the proliferation of MCF-7 (human breast cancer cells), HepG2 (human hepatoma cells), A549 (human lung carcinoma cells), and BxPC-3 (human pancreatic carcinoma cells) tumor cell lines. Furthermore, the compounds also significantly inhibited the release of inflammatory cytokines, including nitric oxide (NO), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß) in the lipopolysaccharide (LPS)-activated mouse cells (RAW 264.7). Among them, compound 2 demonstrated promising broad-spectrum antiproliferative potential with half inhibitory concentration (IC50) values ranging from 5.57 to 8.74 µM and it significantly decreased caspase-3 and Bcl-2 expression in HepG2 cells. These interesting findings show that derivatization of magnolol and honokiol with 1,3,5-triazine affects and modulates their biological properties.

Lipidomics Analysis of Timosaponin BII in INS-1 Cells Induced by Glycolipid Toxicity and Its Relationship with Inflammation.

Anemarrhena asphodeloides Bunge is a traditional Chinese medicine. The timosaponin BII is one of the most abundant and widely studied active ingredients in Anemarrhena asphodeloides Bunge. Related studies have shown that timosaponin BII has potential value for development and further utilization. The protective effect of timosaponin BII on islet ß cells under type 2 diabetes was investigated in the glycolipid toxic INS-1 cell model and possible biomarkers were explored by lipidomics analysis. Timosaponin BII was isolated from Anemarrhena asphodeloides Bunge by polyamide resin and Sephadex LH-20. Then, the glycolipid toxicity INS-1 cell model was established to investigate the protective effect of timosaponin BII. The results showed that timosaponin BII could significantly influence the levels of malondialdehyde (MDA) and glutathione (GSH), thereby restoring the insulin secretion ability and cell viability of model cells. Lipidomics analysis was combined with multivariate statistical analysis for marker selection. The four most common pathological and pharmacological lipid markers were phosphatidylserine (PS), suggesting that timosaponin BII had protective effects on model cells related to the reduction oxidative stress and macrophage inflammation. RAW264.7 macrophages were stimulated by LPS to establish a model of inflammation and study the effect of timosaponin BII on the nodes of NOD-like receptor P3 (NLRP3) inflammasome pathway in the model cells. In conclusion, timosaponin BII may have the effect of protecting INS-1 pancreatic ß cells through reducing IL-1ß (interleukin-1ß) production by inhibiting the NLRP3 inflammasome in macrophage and restoring the insulin secretion ability and cell viability by reducing oxidative stress.

Inhibition of autophagy by hydroxychloroquine enhances antioxidant nutrients and delays postharvest fruit senescence of Ziziphus jujuba.

Autophagy, a mechanism of recycling intracellular constituents, favors plant growth, especially under nutrient starvation. However, autophagy's role in regulating postharvest fruit senescence is unclear. Here, effects of the autophagy inhibitor hydroxychloroquine (HCQ) and activator LiCl on postharvest jujube fruit senescence were investigated. HCQ significantly reduced weight loss and decay incidence, and enhanced firmness compared with those of the control. LiCl had the opposite effects. Protein oxidation and H2O2 increased significantly in LiCl-treated compared with HCQ-treated fruit. The contents of vitamin C, total thiol, and phenolics, and total antioxidant capacity and DPPH-radical scavenging capacity, followed the order: HCQ > control > LiCl. The HCQ-mediated reduction in fruit respiration was significantly enhanced by ATP and partly reversed by 2,4-dinitrophenol, a mitochondrial uncoupler. Thus, jujube fruit senescence may be regulated by autophagy and the antioxidant capacity. A mechanism of autophagy-mediated postharvest fruit senescence involving mitochondrial biogenesis and respiration was proposed.

A pilot-scale, bi-layer bioretention system with biochar and zero-valent iron for enhanced nitrate removal from stormwater.

Nitrogen (N) removal in conventional bioretention systems is highly variable owing to the low nitrate (NO3-) elimination efficiency. We hypothesized that amending bioretention cells with biochar and zero-valent iron (ZVI) could improve the NO3- removal performance. A well-instrumented, bi-layer pilot-scale bioretention cell was developed to test the hypothesis by investigating its hydrologic performance and NO3- removal efficacy as affected by biochar and ZVI amendments. The cell containing 18% (v/v) wood biochar in the vadose zone and 10% (v/v) ZVI in the saturation zone was monitored for 18 months of field infiltration tests using synthetic stormwater amended with bromide (tracer) and NO3-. Compared to the Control cell without amendments, the Biochar/ZVI cell increased water retention by 11-27% and mean residence time by 0.7-3.8 h. The vadose zone of the Biochar/ZVI cell removed 30.6-95.7% (0.6-12.7 g) of NO3-N from the influent, as compared with -6.1-89.6% (-0.1-2.9 g) by that of the Control cell. While the performance varied with synthetic storm events and seasons, in all cases the Biochar/ZVI cell resulted in greater NO3- removal than the Control cell. This improvement was presumably due to biochar's ability to improve water retention, facilitate anoxic conditions, increase residence time, and provide electrons for microbial denitrification. The saturation zone with ZVI amendment further promoted NO3- removal: removal was 1.8 times greater relative to the control in the first infiltration test, but was minimal in following tests. The reduction in performance of the ZVI amendment in subsequent tests might be due to diminished NO3-N input to the saturation zone after treatment by the biochar-amended vadose zone. The redox potential and dissolved oxygen content at the vadose/saturation zone interface also indicated more favorable denitrification conditions in the Biochar/ZVI cell. Biochar amendment demonstrated significant promise for increasing nitrate removal in bioretention systems.

Transcriptome analysis of genes involved in defense against alkaline stress in roots of wild jujube (Ziziphus acidojujuba).

Wild jujube (Ziziphus acidojujuba Mill.) is highly tolerant to alkaline, saline and drought stress; however, no studies have performed transcriptome profiling to study the response of wild jujube to these and other abiotic stresses. In this study, we examined the tolerance of wild jujube to NaHCO3-NaOH solution and analyzed gene expression profiles in response to alkaline stress. Physiological experiments revealed that H2O2 content in leaves increased significantly and root activity decreased quickly during alkaline of pH 9.5 treatment. For transcriptome analysis, wild jujube plants grown hydroponically were treated with NaHCO3-NaOH solution for 0, 1, and 12 h and six transcriptomes from roots were built. In total, 32,758 genes were generated, and 3,604 differentially expressed genes (DEGs) were identified. After 1 h, 853 genes showed significantly different expression between control and treated plants; after 12 h, expression of 2,856 genes was significantly different. The expression pattern of nine genes was validated by quantitative real-time PCR. After gene annotation and gene ontology enrichment analysis, the genes encoding transcriptional factors, serine/threonine-protein kinases, heat shock proteins, cysteine-like kinases, calmodulin-like proteins, and reactive oxygen species (ROS) scavengers were found to be closely involved in alkaline stress response. These results will provide useful insights for elucidating the mechanisms underlying alkaline tolerance in wild jujube.

Iron uptake, translocation and regulation in rice.

Iron is essential for growth and development of rice, which is able to take up Fe3+-phytosiderophore, Fe2+-nicotianamine and free Fe2+. Researchers have uncovered key molecular components including transporters, enzymes, and chelators involved in iron uptake and translocation, as well as factors regulating the expression of these genes in rice. Manipulation of these molecular components has produced transgenic rice with enhanced tolerance to alkaline stress on calcareous soils with low-Fe availability due to high soil pH. In this review, we mainly summarize the molecular mechanisms of iron uptake, translocation, and regulation in rice, and discuss some perspectives of this field.

ALT1, a Snf2 family chromatin remodeling ATPase, negatively regulates alkaline tolerance through enhanced defense against oxidative stress in rice.

Alkaline salt stress adversely affects rice growth, productivity and grain quality. However, the mechanism underlying this process remains elusive. We characterized here an alkaline tolerant mutant, alt1 in rice. Map-based cloning revealed that alt1 harbors a mutation in a chromatin remodeling ATPase gene. ALT1-RNAi transgenic plants under different genetic background mimicked the alt1 phenotype, exhibiting tolerance to alkaline stress in a transcript dosage-dependent manner. The predicted ALT1 protein belonged to the Ris1 subgroup of the Snf2 family and was localized in the nucleus, and transcription of ALT1 was transiently suppressed after alkaline treatment. Although the absorption of several metal ions maintained well in the mutant under alkaline stress, expression level of the genes involved in metal ions homeostasis was not altered in the alt1 mutant. Classification of differentially expressed abiotic stress related genes, as revealed by microarray analysis, found that the majority (50/78) were involved in ROS production, ROS scavenging, and DNA repair. This finding was further confirmed by that alt1 exhibited lower levels of H2O2 under alkaline stress and tolerance to methyl viologen treatment. Taken together, these results suggest that ALT1 negatively functions in alkaline tolerance mainly through the defense against oxidative damage, and provide a potential two-step strategy for improving the tolerance of rice plants to alkaline stress.

Converting poultry litter to activated carbon: optimal carbonization conditions and product sorption for benzene.

To promote utilization of poultry litter as a source material for manufacturing low-cost activated carbon (AC) that can be used in wastewater treatment, this study investigated optimal production conditions and water-borne organic sorption potential of poultry litter-based AC. Pelletized broiler litter was carbonized at different temperatures for varied time periods and activated with steam at a range of flow rate and time. The AC products were examined for quality characteristics using standard methods and for organic sorption potentials using batch benzene sorption techniques. The study shows that the yield and quality of litter AC varied with production conditions. The optimal production conditions for poultry litter-based AC were carbonization at 700 degrees C for 45 min followed by activation with 2.5 ml min(-1) steam for another 45 min. The resulting AC possessed an iodine number of 454 mg g(-1) and a specific surface area of 403 m2 g(-1). It sorbed benzene in water following sigmoidal kinetic and isothermal patterns. The sorption capacity for benzene was 23.70 mg g(-1), lower than that of top-class commercial AC. The results, together with other reported research findings, suggest that poultry litter is a reasonable feedstock for low-cost AC applicable to pre-treat wastewater contaminated by organic pollutants and heavy metals.

Sorption properties of greenwaste biochar for two triazine pesticides.

Biochar is a carbon-rich product generated from biomass through pyrolysis. This study evaluated the ability of an unmodified biochar to sorb two triazine pesticides - atrazine and simazine, and thereby explored potential environmental values of biochar on mitigating pesticide pollution in agricultural production and removing contaminants from wastewater. A greenwaste biochar was produced by heating waste biomass under the oxygen-limited condition at 450 degrees C. The effects of several experimental parameters, including biochar particle size, contact time, solid/solution ratio, and solution pH on the sorption of atrazine and simazine were comprehensively investigated. The biochar with small particle size needed less time to reach sorption equilibrium. The sorption affinity of the biochar for the two pesticides increased with decreasing solid/solution ratio. The sorbed amounts (C(s)) of atrazine and simazine increased from 451 to 1158 mg/kg and 243 to 1066 mg/kg, respectively, when the solid/solution ratio decreased from 1:50 to 1:1000 (g/mL). The sorption of the biochar for both pesticides was favored by low pH. The sorption isotherms of atrazine and simazine on the biochar are nonlinear and follow a Freundlich model. When atrazine and simazine co-existed, a competitive sorption occurred between these two pesticides on the biochar, reflecting a decrease in sorption capacity (K(f)) from 435 to 286 for atrazine and from 514 to 212 for simazine. Combined adsorption and partition mechanisms well depicted sorption of atrazine and simazine on carbonized and noncarbonized fractions of the biochar in the single-solute and co-solute systems.