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BACKGROUND: Our previous studies demonstrated that the administration of crude Polysaccharide from Panax notoginseng (CPPN) can effectively prolong the lifespan of tumor-bearing mice via boosting the host immune system as well as weak cytotoxicity against hepatocellular carcinoma (HCC). In the present study, Neutral Polysaccharide (NPPN) were further purified from crude polysaccharide isolated from panax notoginseng. The effects of NPPN on the immune function and hematopoietic function of mice with low immunity and myelosuppression induced by cyclophosphamide (CTX) were investigated. The effect of NPPN combined with CTX on the tumor inhibition rate of the H22 tumor-bearing mice and the impact of NPPN on the proliferation of H22 liver cancer cells in vitro were investigated. METHODS: CPPN was obtained by water extraction and alcohol precipitation method, and further purified by DEAE Sepharose Fast Flow ion exchange resin column. NPPN was added to the immunosuppressed with myelosuppression mice induced by CTX. Thymus index, spleen index, lymphocyte proliferation stimulation index by adding of concanavalin A, determination of serum hemolysin, NK cell activity assay, mice carbon clearance experiment, blood count tests were detected. The tumor inhibition rate of the H22 tumor-bearing mice treated with NPPN combined with CTX was recorded. RESULTS: NPPN and 4 kinds of acid polysaccharide from Panax notoginseng (APPN) were successfully isolated from the CPPN by DEAE Sepharose Fast Flow ion exchange resin column. NPPN inhibited the growth of H22 cells and significantly increase the tumor inhibition rate of the H22 tumor-bearing mice combined with CTX. The elevation of the cellular and humoral immunity levels as well as a variety of blood count tests indicators of immunosuppressive with myelosuppression mice may contribute to the antitumor activity of NPPN. CONCLUSION: NPPN has a potential antitumor activity for the treatment of liver cancer combined with cyclophosphamide.
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Carcinoma Hepatocelular/tratamento farmacológico , Ciclofosfamida/farmacologia , Sinergismo Farmacológico , Panax notoginseng/química , Extratos Vegetais/farmacologia , Polissacarídeos/farmacologia , Animais , Antineoplásicos Alquilantes/farmacologia , Apoptose , Carcinoma Hepatocelular/patologia , Proliferação de Células , Feminino , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Camundongos , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
All previously reported C70 isomers have positive curvature and contain 12 pentagons in addition to hexagons. Herein, we report a new C70 species with two negatively curved heptagon moieties and 14 pentagons. This unconventional heptafullerene[70] containing two symmetric heptagons, referred to as dihept-C70 , grows in the carbon arc by a theoretically supported pathway in which the carbon cluster of a previously reported C66 species undergoes successive C2 insertion via a known heptafullerene[68] intermediate with low energy barriers. As identified by X-ray crystallography, the occurrence of heptagons facilitates a reduction in the angle of the π-orbital axis vector in the fused pentagons to stabilize dihept-C70 . Chlorination at the intersection of a heptagon and two adjacent pentagons can greatly enlarge the HOMO-LUMO gap, which makes dihept-C70 Cl6 isolable by chromatography. The synthesis of dihept-C70 Cl6 offers precious clues with respect to the fullerene formation mechanism in the carbon-clustering process.
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Chronic obstructive pulmonary disease (COPD) is a respiratory inflammatory disease. Psoralen (PSO) is the main pharmacological component identified from Bu-Shen-Fang-Chuan formula which has been traditionally used in treatment of COPD, yet its efficacy in COPD inflammation were unreported. In this study, we aimed to elucidate the anti-inflammatory potential of PSO in COPD and unravel the underlying mechanisms, focusing on T lymphocyte recruitment and the modulation of chemokines, namely monokine induced by interferon-gamma (CXCL9), interferon inducible protein 10 (CXCL10), and interferon inducible T-Cell alpha chemoattractant (CXCL11). In vitro, RAW264.7 was stimulated by interferon (IFN)-γ + cigarette smoke extract (CSE) and were treated with PSO (2.5, 5, 10 µM), then the levels of chemokines and the activation of Janus kinase (JAK)/Signal transducer and activator of transcription 1 (STAT1) pathway were analyzed by real time PCR and western blot. In vivo, a murine model was established by intraperitoneal injection of CSE on day 1, 8, 15, and 22, then treated with PSO (10 mg/kg). Our experiments in vitro illustrated that PSO reduced the levels of CXCL9, CXCL10, and CXCL11, and decreased the protein phosphorylation levels of JAK2 and STAT1. Additionally, PSO effectively improved inflammatory infiltration and decreased the proportion of CD8+ T cells in CSE-exposed mice. Furthermore, PSO reduced the levels of CXCL9, CXCL10, and CXCL11 in bronchoalveolar lavage fluid (BALF) and lung tissue, and decreased the protein phosphorylation levels of JAK2 and STAT1. In conclusion, our results revealed the therapeutic potential of PSO for COPD inflammation, possibly mediated through the regulation of CD8+ T cell recruitment and chemokines via the JAK2/STAT1 signaling pathway.
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The discovery of novel antitumor agents derived from natural plants is a principal objective of anticancer drug research. Frankincense, a widely recognized natural antitumor medicine, has undergone a systematic review encompassing its species, chemical constituents, and diverse pharmacological activities and mechanisms. The different species of frankincense include Boswellia serrata, Somali frankincense, Boswellia frereana, and Boswellia arabica. Various frankincense extracts and compounds exhibit antitumor, anti-inflammatory, and hepatoprotective properties and antioxidation, memory enhancement, and immunological regulation capabilities. They also have comprehensive effects on regulating flora. Frankincense and its principal chemical constituents have demonstrated promising chemoprophylactic and therapeutic abilities against tumors. This review provides a systematic summary of the mechanism of action underlying the antitumor effects of frankincense and its major constituents, thus laying the foundations for developing effective tumor-combating targets.
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Franquincenso , Humanos , Franquincenso/química , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Animais , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Extratos Vegetais/químicaRESUMO
Background: Infantile hemangiomas (IH) and venous malformations (VM) are the most common types of vascular abnormalities that seriously affect the health of children. Although there is evidence that these two diseases share some common genetic changes, the underlying mechanisms need to be further studied. Methods: The microarray datasets of IH (GSE127487) and VM (GSE7190) were downloaded from GEO database. Extensive bioinformatics methods were used to investigate the common differentially expressed genes (DEGs) of IH and VM, and to estimate their Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Trough the constructing of protein-protein interaction (PPI) network, gene models and hub genes were obtained by using Cytoscape and STRING. Finally, we analyzed the co-expression and the TF-mRNA-microRNA regulatory network of hub genes. Results: A total of 144 common DEGs were identified between IH and VM. Functional analysis indicated their important role in cell growth, regulation of vasculature development and regulation of angiogenesis. Five hub genes (CTNNB1, IL6, CD34, IGF2, MAPK11) and two microRNA (has-miR-141-3p, has-miR-150-5p) were significantly differentially expressed between IH and normal control (p < 0.05). Conclusion: In conclusion, our study investigated the common DEGs and molecular mechanism in IH and VM. Identified hub genes and signaling pathways can regulate both diseases simultaneously. This study provides insight into the crosstalk of IH and VM and obtains several biomarkers relevant to the diagnosis and pathophysiology of vascular abnormalities.
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OBJECTIVE: Childhood obesity is a major health concern worldwide. Previous studies have explored the relationship between obesity and gut microbiota. However, the results from such studies remain contradictory. METHODS: In the present nested case-control study, based on a twin birth cohort study, the relationship between gut microbiota diversity and overweight/obesity in 1- and 6-month-old infants was explored. Twins were enrolled when one child had normal weight and the other child was overweight/obese at six months old. For both infants, stool samples were collected at 1 and 6 months of age. Finally, 12 twins were enrolled in the study. The gut microbiota was identified by 16S rRNA gene sequencing in the V3-V4 area. Six of the twins were monozygotic. RESULTS: The results revealed that the microbiota communities of monozygotic twins were similar to those of dizygotic twins. The relative abundance (RA) of microbiota of 1-month-old twins was significantly higher than that of 6-month-old twins. However, the microbiota diversity of 1-month-old twins was significantly lower than that of 6-month-old twins. In addition, 6-month-old twins had significantly higher RA levels of Bifidobacterium and Lachnospiracea incertae sedis than 1-month-old twins. The 6-month-old group had significantly lower RA levels of Veillonella, Klebsiella, Akkermansia, Streptococcus, or Staphylococcus than the 1-month-old group. At six months, the RA level of Clostridium sensu stricto was higher in the overweight/obesity group than the normal-weight group. CONCLUSION: These findings imply that changes in gut microbiota diversity during infancy may contribute to the development of obesity in early infancy.
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Microbioma Gastrointestinal , Sobrepeso/microbiologia , Obesidade Infantil/microbiologia , Coorte de Nascimento , Estudos de Casos e Controles , Feminino , Humanos , Lactente , Masculino , RNA Ribossômico 16SRESUMO
Inverted cuttings of Populus yunnanensis are characterized by enlarged stems and dwarfed new shoots, and phytohormones play a crucial role in the response to inversion. The polar auxin transport (PAT) system is distinct from the transport systems of other hormones and is controlled by three major transporter gene families: pin-formed (PIN), auxin-resistant/like aux (AUX/LAX) and ATP-binding cassette transporters of the B class (ABCB). Here, we identified these three families in P. trichocarpa, P. euphratica and P. yunnanensis through a genome-wide analysis. The Populus PIN, AUX/LAX and ABCB gene families comprised 15, 8 and 31 members, respectively. Most PAT genes in Populus and Arabidopsis were identified as clear sister pairs, and some had unique motifs. Transcriptome profiling revealed that the expression of most PAT genes was unrelated to cutting inversion and that only several genes showed altered expression when cuttings were inverted. The auxin content difference at positions was opposite in upright and inverted cutting bodies during rooting, which obeyed the original plant polarity. However, during plant growth, the two direction types exhibited similar auxin movements in the cutting bodies, and the opposite auxin changes were observed in new shoots. Four PAT genes with a positive response to cutting inversion, PyuPIN10, PyuPIN11, PyuLAX6 and PyuABCB27, showed diverse expression patterns between upright and inverted cuttings during rooting and plant growth. Furthermore, PAT gene expression retained its polarity, which differs from the results found for auxin flow during plant growth. The inconformity indicated that a new downward auxin flow in addition to the old upward flow might be established during the growth of inverted cuttings. Some highly polar PAT genes were involved in the maintenance of original auxin polarity, which might cause the enlarged stems of inverted cuttings. This work lays a foundation for understanding the roles of auxin transport in plant responses to inversion.
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Perfilação da Expressão Gênica/métodos , Ácidos Indolacéticos/metabolismo , Proteínas de Membrana Transportadoras/genética , Populus/crescimento & desenvolvimento , Regulação da Expressão Gênica no Desenvolvimento , Regulação da Expressão Gênica de Plantas , Proteínas de Membrana Transportadoras/metabolismo , Família Multigênica , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Populus/classificação , Populus/genética , Populus/metabolismo , Sequenciamento Completo do GenomaRESUMO
The 1,3,5-oxadiazinane ring in the title compound, C(12)H(14)F(2)N(4)O(3), has a conformation inter-mediate between half-chair and screw-boat. The crystal structure is stabilized by weak inter-molecular C-Hâ¯O hydrogen bonds. Weak π-π inter-actions are indicated by the relatively long centroid-centroid distance of 3.9199â (12)â Å and inter-planar distance of 3.803â Å between symmetry-related benzene rings from neighbouring mol-ecules.
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In the title compound, C(12)H(15)ClN(4)O(3), which has potential insecticidal activity, the oxadiazine ring and the benzene ring make a dihedral angle of 84.63â (2)° to one another. The crystal packing involves weak inter-molecular C-Hâ¯O hydrogen bonds.
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PURPOSE: The current study was undertaken to examine the anticancer potential of davanone against human ovarian cancer cells along with evaluating its effects on cell apoptosis, PI3K/AKT/MAPK signaling pathway and cell migration and invasion. METHODS: CCK-8 assay was performed for cell viability and clonogenic potential was examined through clonogenic assay. Acridine orange (AO)/Ethidium bromide (EB) dual staining assay was performed to detect apoptosis and quantification of apoptosis was achieved through annexin V-FITC/propidium iodide (PI) staining assay. Mitochondrial membrane potential (MMP) was studied via flow cytometric analysis of ovarian cancer cells. Cell migration and invasion potential of ovarian cancer cells was monitored via transwell assay. Western blotting technique was used to study PI3K/AKT/MAPK pathway. RESULTS: The results indicated that davanone induced dose as well as time dependent inhibition in cell viability of OVACAR-3 cells. Next, AO/EB staining suggested that the antiproliferative effects of davanone are apoptosis-mediated. There was a remarkable increase in apoptotic cell percentage with the molecule dose. Caspase-3, -8 and -9 activity along with Bax activity were observed to be increasing with davanone doses and Bcl-2 activity decreased with increasing molecule concentration. Transwell assay indicated potential inhibition of invasive and migratory ability of OVACAR-3 cells after davanone exposure. Finally, western blotting analysis revealed that davanone resulted in blocking of PI3K/AKT/MAPK signaling pathway in OVACAR-3 cells. CONCLUSION: The results indicate that davanone is a potential anticancer agent against human ovarian cancer mediated via caspase-dependent apoptosis, loss of MMP, inhibition of cell migration and invasion and targeting PI3K/AKT/MAPK signaling pathway.
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Movimento Celular/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Neoplasias Ovarianas/tratamento farmacológico , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Sesquiterpenos/farmacologia , Apoptose/efeitos dos fármacos , Feminino , Citometria de Fluxo , Humanos , Invasividade Neoplásica , Neoplasias Ovarianas/metabolismo , Transdução de SinaisRESUMO
Inverted cuttings of Populus yunnanensis exhibit an interesting growth response to inversion. This response is characterized by enlargement of the stem above the shoot site, while the upright stem shows obvious outward growth below the shoot site. In this study, we examined transcriptome changes in bark tissue at four positions on upright and inverted cuttings of P. yunnanensis: position B, the upper portion of the stem; position C, the lower portion of the stem; position D, the bottom of new growth; and position E, the top of new growth. The results revealed major transcriptomic changes in the stem, especially at position B, but little alteration was observed in the bark tissue of the new shoot. The differentially expressed genes (DEGs) were mainly assigned to four pathways: plant hormone signal transduction, plant-pathogen interaction, mitogen-activated protein kinase (MAPK) signaling pathway-plant, and adenosine triphosphate-binding cassette (ABC) transporters. Most of these DEGs were involved in at least two pathways. The levels of many hormones, such as auxin (IAA), cytokinin (CTK), gibberellins (GAs), ethylene (ET), and brassinosteroids (BRs), underwent large changes in the inverted cuttings. A coexpression network showed that the top 20 hub unigenes at position B in the upright and inverted cutting groups were associated mainly with the BR and ET signaling pathways, respectively. Furthermore, brassinosteroid insensitive 1-associated receptor kinase 1 (BAK1) in the BR pathway and both ethylene response (ETR) and constitutive triple response 1 (CTR1) in the ET pathway were important hubs that interfaced with multiple pathways.
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Inverted cuttings of Populus yunnanensis remain alive by rooting from the original morphological apex and sprouting from the base, but the lateral branches exhibit less vigorous growth than those of the upright plant. In this study, we examined the changes in hormone contents, oxidase activities, and transcriptome profiles between upright and inverted cuttings of P. yunnanensis. The results showed that the indole-3-acetic acid (IAA) and gibberellic acid (GA3) contents were significantly lower in inverted cuttings than in upright cuttings only in the late growth period (September and October), while the abscisic acid (ABA) level was always similar between the two direction types. The biosynthesis of these hormones was surprisingly unrelated to the inversion of P. yunnanensis during the vegetative growth stage (July and August). Increased levels of peroxidases (PODs) encoded by 13 differentially expressed genes (DEGs) served as lignification promoters that protected plants against oxidative stress. Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis showed that most DEGs (107) were related to carbohydrate metabolism. Furthermore, altered activities of uridine diphosphate (UDP)-sugar pyrophosphorylase (USP, 15 DEGs) for nucleotide sugars, pectin methylesterase (PME, 7 DEGs) for pectin, and POD (13 DEGs) for lignin were important factors in the response of the trees to inversion, and these enzymes are all involved cell wall metabolism.
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Endophytic fungi from the fruit of Pteroceltis tatarinowii were studied, to understand the characteristics of microbial community composition on this ancient and peculiar wild plant. Healthy fruits were collected from areas of the natural distribution of P. tatarinowii in Langyashan Natural Reserve, Anhui Province, China. Endophytic fungi were isolated from fruit tissue, and fungal strains were classified on the basis of morphology. From 500 tissue blocks taken from fruit, a total of 428 isolates of endophytic fungi were identified and classified into 20 genera, 4 families, and 3 orders. Eighty strains showed no reproductive structures, and were classified as Mycelia sterilia (18.7%). The dominant families were Dematiaceae and Sphaeropsidaceae, occupying 38.1% and 32.9% of isolates, respectively. Alternaria and Phomopsis were the dominant genera, accounting for 27.1% and 16.8% of isolates. Different parts of the fruit had different compositions of endophytes. The highest number of fungi was isolated from seeds (19 genera, 181 strains, 42.3%), and the lowest from fruiting wings (7 genera, 88 strains, 20.6%). Alternaria was the commonest genus of endophytes, isolated from three different parts of the fruit. Phomopsis and Macrophoma were the dominant genera on carpopodium and fruiting wings, respectively. The communities on carpopodium and fruiting wings were most similar to one another (CS=0.78), while those on fruiting wings and seeds were least similar (CS=0.50). Fisher's exact test showed no significant difference between the compositions of endophytes from the carpopodium and fruiting wings, while significant diffe-rences were observed between communities on seed and carpopodium, and seed and fruiting wings.