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Cyathus olla, belonging to the genus Cyathus within the order Agaricales, is renowned for its bird's nest-like fruiting bodies and has been utilized in folk medicine. However, its genome remains poorly understood. To investigate genomic diversity within the genus Cyathus and elucidate biosynthetic pathways for medicinal compounds, we generated a high-quality genome assembly of C. olla with fourteen chromosomes. The comparative genome analysis revealed variations in both genomes and specific functional genes within the genus Cyathus. Phylogenomic and gene family variation analyses provided insights into evolutionary divergence, as well as genome expansion and contraction in individual Cyathus species and 36 typical Basidiomycota. Furthermore, analysis of LTR-RT and Ka/Ks revealed apparent whole-genome duplication (WGD) events its genome. Through genome mining and metabolite profiling, we identified the biosynthetic gene cluster (BGC) for cyathane diterpenes from C. olla. Furthermore, we predicted 32 BGCs, containing 41 core genes, involved in other bioactive metabolites. These findings represent a valuable genomic resource that will enhance our understanding of Cyathus species genetic diversity. The genome analysis of C. olla provides insights into the biosynthesis of medicinal compounds and establishes a fundamental basis for future investigations into the genetic basis of chemodiversity in this significant medicinal fungus.
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Genoma Fúngico , Familia de Multigenes , Filogenia , Vías Biosintéticas/genética , Agaricales/genética , Agaricales/metabolismo , Diterpenos/metabolismo , Genómica , MetabolomaRESUMEN
The Chinese medicinal fungi "Sanghuang" have been long recognized for their significant and valued medicinal properties, as documented in ancient medical literature. However, in traditional folk medicine, various macrofungi sharing similar appearance, habitat, and therapeutic effects with Sanghuang were erroneously used. These Sanghuang-like fungi mainly belong to the Porodaedalea, Phellinus, and Inonotus genera within the Hymenochaetaceae family. Despite the establishment of the Sanghuangporus genus and the identification of multiple species, the emerging taxonomic references based on morphological, ITS, and mycelial structural features have been inadequate to differentiate Sanghuangporus and Sanghuang-like fungi. To address this limitation, this study presents the first comparative and phylogenetic analysis of Sanghuang-related fungi based on mitogenomes. Our results show that Sanghuangporus species show marked convergence in mitochondrial genomic features and form a distinct monophyletic group based on phylogenetic analyses of five datasets. These results not only deepen our understanding of Sanghuang-like fungi but also offer novel insights into their mitochondrial composition and phylogeny, thereby providing new research tools for distinguishing members of the Sanghuangporus genus. KEY POINTS: ⢠Sanghuangporus, Inonotus, and Porodaedalea are monophyly in sanghuang-like species. ⢠Mitogenome-based analysis exhibits high resolution in sanghuang-like genus. ⢠The mitogenomes provide strong evidence for reclassifying Phellinus gilvus S12 as Sanghuangporus vaninii.
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Filogenia , Genoma Mitocondrial , Basidiomycota/genética , Basidiomycota/clasificación , ADN de Hongos/genética , Medicina Tradicional China , Análisis de Secuencia de ADNRESUMEN
Actinomycetes are remarkable natural sources of active natural molecules and enzymes of considerable industrial value. Streptomyces mobaraensis is the first microorganism found to produce transglutaminase with broad industrial applications. Although transglutaminase in S. mobaraensis has been well studied over the past three decades, the genome of S. mobaraensis and its secondary metabolic potential were poorly reported. Here, we presented the complete genome of S. mobaraensis DSM40587 obtained from the German Collection of Microorganisms and Cell Cultures GmbH. It contains a linear chromosome of 7,633,041 bp and a circular plasmid of 23,857 bp. The chromosome with an average GC content of 73.49% was predicted to harbour 6683 protein-coding genes, seven rRNA and 69 tRNA genes. Comparative genomic analysis reveals its meaningful genomic characterisation. A comprehensive bioinformatics investigation identifies 35 putative BGCs (biosynthesis gene clusters) involved in synthesising various secondary metabolites. Of these, 13 clusters showed high similarity (> 55%) to known BGCs coding for polyketides, nonribosomal peptides, hopene, RiPP (Ribosomally synthesized and post-translationally modified peptides), and others. Furthermore, these BGCs with over 65% similarity to the known BGCs were analysed in detail. The complete genome of S. mobaraensis DSM40587 reveals its capacity to yield diverse bioactive natural products and provides additional insights into discovering novel secondary metabolites.
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The family Nidulariaceae, consisting of five genera including Cyathus, is a unique group of mushrooms commonly referred to as bird's nest fungi due to their striking resemblance to bird's nests. These mushrooms are considered medicinal mushrooms in Chinese medicine and have received attention in recent years for their anti-neurodegenerative properties. However, despite the interest in these mushrooms, very little is known about their mitochondrial genomes (mitogenomes). This study is the first comprehensive investigation of the mitogenomes of five Nidulariaceae species with circular genome structures ranging in size from 114,236 bp to 129,263 bp. Comparative analyses based on gene content, gene length, tRNA, and codon usage indicate convergence within the family Nidulariaceae and heterogeneity within the order Agaricales. Phylogenetic analysis based on a combined mitochondrial conserved protein dataset provides a well-supported phylogenetic tree for the Basidiomycetes, which clearly demonstrates the evolutionary relationships between Nidulariaceae and other members of Agaricales. Furthermore, phylogenetic inferences based on four different gene sets reveal the stability and proximity of evolutionary relationships within Agaricales. These results reveal the uniqueness of the family Nidulariaceae and its similarity to other members of Agaricales; provide valuable insights into the origin, evolution, and genetics of Nidulariaceae species; and enrich the fungal mitogenome resource. This study will help to expand the knowledge and understanding of the mitogenomes in mushrooms.
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Agaricales , Genoma Mitocondrial , Agaricales/genética , Filogenia , Genoma Mitocondrial/genética , Intrones/genética , Reordenamiento Génico , Proteínas MitocondrialesRESUMEN
Patients with abdominopelvic cancer undergoing radiotherapy commonly develop radiation-induced intestinal injury (RIII); however, its underlying pathogenesis remains elusive. The von Willebrand factor (vWF)/a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) axis has been implicated in thrombosis, inflammation, and oxidative stress. However, its role in RIII remains unclear. In this study, the effect of radiation on vWF and ADAMTS13 expression was firstly evaluated in patients with cervical cancer undergoing radiotherapy and C57BL/6J mice exposed to different doses of total abdominal irradiation. Then, mice with the specific deletion of vWF in the platelets and endothelium were established to demonstrate the contribution of vWF to RIII. Additionally, the radioprotective effect of recombinant human (rh) ADAMTS13 against RIII was assessed. Results showed that both the patients with cervical cancer undergoing radiotherapy and RIII mouse model exhibited increased vWF levels and decreased ADAMTS13 levels. The knockout of platelet- and endothelium-derived vWF rectified the vWF/ADAMTS13 axis imbalance; improved intestinal structural damage; increased crypt epithelial cell proliferation; and reduced radiation-induced apoptosis, inflammation, and oxidative stress, thereby alleviating RIII. Administration of rhADAMTS13 could equally alleviate RIII. Our results demonstrated that abdominal irradiation affected the balance of the vWF/ADAMTS13 axis. vWF exerted a deleterious role and ADAMTS13 exhibited a protective role in RIII progression. rhADAMTS13 has the potential to be developed into a radioprotective agent.
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Neoplasias del Cuello Uterino , Factor de von Willebrand , Femenino , Humanos , Ratones , Animales , Factor de von Willebrand/genética , Factor de von Willebrand/química , Factor de von Willebrand/metabolismo , Ratones Endogámicos C57BL , Inflamación/prevención & control , Estrés OxidativoRESUMEN
Agaricus bitorquis, an emerging wild mushroom with remarkable biological activities and a distinctive oversized mushroom shape, has gained increasing attention in recent years. Despite its status as an important resource of wild edible fungi, knowledge about this mushroom is still limited. In this study, we used the Illumina NovaSeq and Nanopore PromethION platforms to sequence, de novo assemble, and annotate the whole genome and mitochondrial genome (mitogenome) of the A. bitorquis strain BH01 isolated from Bosten Lake, Xinjiang Province, China. Using the genome-based biological information, we identified candidate genes associated with mating type and carbohydrate-active enzymes in A. bitorquis. Cluster analysis based on P450 of basidiomycetes revealed the types of P450 members of A. bitorquis. Comparative genomic, mitogenomic, and phylogenetic analyses were also performed, revealing interspecific differences and evolutionary features of A. bitorquis and A. bisporus. In addition, the molecular network of metabolites was investigated, highlighting differences in the chemical composition and content of the fruiting bodies of A. bitorquis and A. bisporus. The genome sequencing provides a comprehensive understanding and knowledge of A. bitorquis and the genus Agaricus mushrooms. This work provides valuable insights into the potential for artificial cultivation and molecular breeding of A. bitorquis, which will facilitate the development of A. bitorquis in the field of edible mushrooms and functional food manufacture.
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Two previously undescribed natural cyathane diterpenoids Me-dentifragilin A (1) and Epi-neocyathin O (2), and three known cyathane diterpenoids 3-5, cyathin O, neocyathin P, and cyathin I, were isolated from the rice medium of the Cyathus striatus CBPFE A06. Their structures were established by NMR spectra, and HR-ESI-MS. Compounds 1-5 displayed encouraging neurotrophic activity in PC-12 cells at doses of 5 µM. Meanwhile, 1-5 significantly inhibited LPS-induced NO generation in BV2 cells with the IC50 values ranging from 2.44 ± 0.16 to 4.33 ± 0.32 µM. Western blot analysis showed that 2 and 4 inhibited the expression of genes involved in nitric oxide (NO) production. Molecular docking revealed that five residues of inducible NO synthase (iNOS) are key residues affecting the interaction of 2 and 4 with iNOS. This study enriches the structural diversity of cyathane diterpenes and adds to the evidence that cyathane diterpenes prevent and treat neurodegenerative diseases.
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SCOPE: Gastrointestinal toxicity is one of the major side effects of abdominopelvic tumor radiotherapy. Studies have shown that perillaldehyde (PAH) has antioxidant, antiinflammatory, antimicrobial activity, and antitumor effects. This study aims to determine whether PAH has radioprotective effects on radiation-induced intestinal injury and explore the underlying mechanisms. METHODS AND RESULTS: C57BL/6J mice are gavaged with PAH for 7 days, then exposed to a single dose of 13 Gy X-ray total abdominal irradiation (TAI). PAH treatment prolongs the survival time, promotes the survival of crypt cells, attenuates radiation-induced DNA damage, and mitigates intestinal barrier damage in the irradiated mice. PAH also shows radioprotective effects in intestinal crypt organoids and human intestinal epithelial cells (HIEC-6). PAH-mediated radioprotection is associated with the upregulation of nuclear factor erythroid-2 related factor 2 (Nrf2), activation of the antioxidant pathway, and inhibition of ferroptosis. Notably, treatment with the Nrf2 inhibitor ML385 abolishes the protective effects of PAH, indicating that Nrf2 activation is essential for PAH activity. CONCLUSION: PAH inhibits ionizing radiation (IR)-induced ferroptosis and attenuates intestinal injury after irradiation by activating Nrf2 signaling. Therefore, PAH is a promising therapeutic strategy for IR-induced intestinal injury.
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The prevalence of superbugs, represented by methicillin-resistant Staphylococcus aureus (MRSA), has become a serious clinical and public safety concern with rising incidence in hospitals. Polyketides with diverse chemical structures harbor many antimicrobial activities, including those of rifampin and rapamycin against MRSA. Streptomyces sp. QHH-9511 was isolated from a niche habitat in the Qinghai-Tibet Plateau and used to produce antibacterial metabolites. Herein, an integrated approach combining genome mining and metabolic analysis were employed to decipher the chemical origin of the antibacterial components with pigmented properties in strain QHH-9511, a novel Streptomyces species from a lichen symbiont on the Qinghai-Tibet Plateau. Genomic phylogeny assembled at the chromosome level revealed its unique evolutionary state. Further genome mining uncovered 36 candidate gene clusters, most of which were uncharacterized. Meanwhile, based on liquid chromatography coupled to diode array detection mass spectrometry, a series of granaticins, BSMs, chromones, phaeochromycins, and related molecules were discovered by using the Global Natural Product Social molecular networking platform. Subsequently, several pigment compounds were isolated and identified by high-resolution mass spectrometry and/or nuclear magnetic resonance, among which the structure-activity relationships of seven aromatic polyketides showed that the fused lactone ring of the C-2 carboxyl group could increase antibacterial activity. Genetic experiments indicated that all seven aromatic polyketides are a series of metabolic shunts produced by a single type II polyketide synthase (PKS) cluster. Comparative genomic analysis of granaticin producers showed that the granaticin gene cluster is widely distributed. This study provides an efficient method to combine genome mining and metabolic profiling techniques to uncover bioactive metabolites derived from specific habitats, while deepening our understanding of aromatic polyketide biosynthesis. IMPORTANCE Undescribed microorganisms from special habitats are being screened for anti-superbug drug molecules. In a project to screen actinomycetes for anti-MRSA activity, we isolated a Streptomyces strain from Qinghai Lake lichens. The phylogeny based on the genome assembled at the chromosome level revealed this strain's unique evolutionary state. The chemical origins of the antibacterial components with pigment properties in strain QHH-9511 were determined using an integrated approach combining genome mining and metabolic analysis. Further genome mining uncovered 36 secondary metabolite gene clusters, the majority of which were previously unknown. A series of aromatic compounds were discovered using molecular network analysis, separation, and extraction. Genetic experiments revealed that all seven aromatic polyketides are a series of metabolic shunts produced by a single cluster of type II PKSs. This study describes a method for identifying novel Streptomyces from specific habitats by combining genome mining with metabolic profiling techniques.
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Staphylococcus aureus Resistente a Meticilina , Policétidos , Streptomyces , Streptomyces/genética , Streptomyces/metabolismo , Staphylococcus aureus Resistente a Meticilina/genética , Staphylococcus aureus Resistente a Meticilina/metabolismo , Tibet , Antibacterianos/farmacología , Antibacterianos/metabolismo , Policétidos/química , Policétidos/metabolismo , Genómica , FilogeniaRESUMEN
In the original publication, there were publisher errors in the names of authors Zhen-xin Wang, Xi-long Feng and Jin-ming Gao and affiliation (1) of the first, second, fourth and fifth authors (name of the Key Laboratory and city) [...].
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Inonotus hispidus mushroom is a popular edible and medicinal mushroom with a long history of use. It is well known as a medicinal fungus with various health benefits for its significant anticancer and immunomodulatory activities. Over the last 60 years, secondary metabolites derived from I. hispidus and their biological activities have been discovered and investigated. Structurally, these compounds are mainly polyphenols and triterpenoids, which have anticancer, anti-inflammatory, antioxidant, antimicrobial, and enzyme inhibitor activities. Here, the secondary metabolites derived from I. hispidus and their activities were systematically and comprehensively classified and summarized, and the biosynthetic pathway of stylylpyrones was deduced and analyzed further. This review contributes to our understanding of I. hispidus and will help with research into natural product chemistry, pharmacology, and the biosynthesis of I. hispidus metabolites. According to this review, I. hispidus could be a promising source of bioactive compounds for health promotion and the development of functional foods.
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Laetiporus sulphureus mushroom is a complementary and alternative medicine that has anticancer, antioxidation, and analgesic effects and immunomodulatory activity; it is used as a treatment for cough and rheumatism and is a functional food that can improve physical fitness. Even though L. sulphureus has garnered considerable biotechnological and pharmacological interest due to its excellent cellulose-degrading ability and diverse biological activities, its biosynthetic potential regarding polysaccharides and secondary metabolites has not been thoroughly examined. In this study, we sequenced and assembled the whole genome of a wild L. sulphureus isolate, NWAFU-1, from the Qinling Mountains in China. Comparative genomes analysis revealed genomic differences between subspecies, and phylogenomic analysis revealed evolutionary divergence as well as genome expansion and contraction of individual Polyporaceae family species. Bioinformatics investigation identified candidate genes associated with mating type, polysaccharide synthesis, carbohydrate-active enzymes, and secondary-metabolite biosynthesis, which included multiple terpenoids, nonribosomal peptides, and polyketides. The locations of biosynthetic core genes were mapped and displayed on chromosomes and contigs. Totals of 143 proteins from 126 coding genes were identified and divided into 14 cytochrome P450 families. Furthermore, the biosynthetic network of tetracyclic triterpenoid active components was postulated by genome mining of related genes combined with the molecular network of metabolites. The genome analysis of L. sulphureus in this study improves the understanding of the biosynthesis of active compounds, which will lay a theoretical foundation for subsequent research on active-compound biosynthesis and promote the application of Laetiporus in the field of drug research and functional-food creation. IMPORTANCE L. sulphureus is a parasitic basidiomycete fungus that causes brown rot. The fruiting bodies of L. sulphureus are used as ancient medicines in China and Europe to cure cancer, analgesia, cough, and rheumatism and are considered a functional food that regulates the body and improves health. L. sulphureus was inferred to be a tetrapolar system based on a high-quality genome, which will aid molecular breeding and artificial farming. Screening polysaccharide synthesis candidate genes and comparing carbohydrate-associated genes in brown-rot basidiomycetes help understand their growth. Identifying core genes for secondary-metabolite biosynthesis, gene cluster family analysis, and comparative cluster analysis will guide heterologous-biosynthesis investigations of these genes and help elucidate the biosynthetic pathways for L. sulphureus bioactive natural components. The biosynthesis network of tetracyclic triterpenes was mapped using metabolite profiling and genome scanning. This work explores the biosynthetic capacity of L. sulphureus-derived natural products and lays the foundation for biosynthetic studies of them.
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Agaricales , Basidiomycota , Productos Biológicos , Policétidos , Enfermedades Reumáticas , Triterpenos , Agaricales/genética , Agaricales/química , Agaricales/metabolismo , Tos/genética , Basidiomycota/genética , Terpenos/metabolismo , Genómica , Cromosomas/metabolismo , Carbohidratos , Enfermedades Reumáticas/genética , Celulosa , AnalgésicosRESUMEN
Inonotus hispidus mushroom is a traditional medicinal fungus with anti-cancer, antioxidation, and immunomodulatory activities, and it is used in folk medicine as a treatment for indigestion, cancer, diabetes, and gastric illnesses. Although I. hispidus is recognized as a rare edible medicinal macrofungi, its genomic sequence and biosynthesis potential of secondary metabolites have not been investigated. In this study, using Illumina NovaSeq combined with the PacBio platform, we sequenced and de novo assembled the whole genome of NPCB_001, a wild I. hispidus isolate from the Aksu area of Xinjiang Province, China. Comparative genomic and phylogenomic analyses reveal interspecific differences and evolutionary traits in the genus Inonotus. Bioinformatics analysis identified candidate genes associated with mating type, polysaccharide synthesis, carbohydrate-active enzymes, and secondary metabolite biosynthesis. Additionally, molecular networks of metabolites exhibit differences in chemical composition and content between fruiting bodies and mycelium, as well as association clusters of related compounds. The deciphering of the genome of I. hispidus will deepen the understanding of the biosynthesis of bioactive components, open the path for future biosynthesis research, and promote the application of Inonotus in the fields of drug research and functional food manufacturing.
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Ferroptosis is a newly recognized form of regulated cell death that is characterized by severe lipid peroxidation initiated by iron overload and the generation of reactive oxygen species (ROS). However, the role of iron in ionizing radiation (IR)-induced intestinal injury has not been fully illustrated yet. In this study, we found that IR induced ferroptosis in intestinal epithelial cells, as indicated by the increase in intracellular iron levels and lipid peroxidation, upregulation of prostaglandin-endoperoxide synthase 2 (PTGS2) mRNA, reduced glutathione peroxidase 4 (GPX4) mRNA and glutathione (GSH) levels, and significant mitochondrial damage. In addition, the iron chelator deferoxamine (DFO) attenuated IR-induced ferroptosis and intestinal injury in vitro and in vivo. Intriguingly, pharmacological inhibition of autophagy with 3-methyladenine (3-MA) mitigated IR-induced ferritin downregulation, iron overload and ferroptosis. IR increased the levels of nuclear receptor coactivator 4 (NCOA4) mRNA and protein. NCOA4 knockdown significantly inhibited the reduction of ferritin, decreased the level of intracellular free iron, and mitigated ferroptosis induced by IR in HIEC cells, indicating that NCOA4-mediated autophagic degradation of ferritin (ferritinophagy) was required for IR-induced ferroptosis. Furthermore, cytoplasmic iron further activated mitoferrin2 (Mfrn2) on the mitochondrial membrane, which in turn increased iron transport into the mitochondria, resulting in increased ROS production and ferroptosis. In addition, mice fed with an iron-deficient diet for 3 weeks showed a significant reversal in the intestinal injury induced by abdominal IR exposure. Taken together, ferroptosis is a novel mechanism of IR-induced intestinal epithelial cytotoxicity, and is dependent on NCOA4-mediated ferritinophagy.
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OBJECTIVE: To evaluate the clinic value of (18)F-FDG PET/CT imaging in differentiation of malignant from benign disease in lung. METHODS: 188 patients underwent (18)F-FDG 45 min early and 2 h delayed PET/CT imaging after intravenous injection of (18)F-FDG. The standardized uptake value (SUV) and retention index (RI) of region of interesting were calculated. The histological diagnosis or clinical findings in a 12 months follow-up period served as the standard of truth. RESULTS: In 114 patients with malignant disease and 74 patients with benign disease, the sensitivity, speciality and accuracy of (18)F-FDG PET/CT imaging in differentiation of malignant from benign lung nodules (diameter more than 10 mm) were 98.2%, 80.0%, and 96.6%, in mediastinal lymph nodes and were 95.7%, 41.7%, and 84.8%, respectively. The sensitivity of (18)F-FDG PET imaging for lung nodules (diameter less than 10 mm) was lower than CT. CONCLUSIONS: Integrated PET/CT imaging provides high sensitivity, specificity and reasonably high accuracy for lung cancer.
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Tomografía de Emisión de Positrones , Radiofármacos , Fluorodesoxiglucosa F18 , Humanos , Neoplasias Pulmonares , Tomografía Computarizada por Rayos XRESUMEN
Application of controlled-release nitrogenous fertilizers can improve the efficiency of fertilizers and reduce the environmental pollution. Controlled-release urea (coated urea) is one of the controlled-release nitrogenous fertilizers developed quickly in the recent years. The rate of controlled-release urea pervasion through membrane is the most important index of the capacity of controlled release. There is a maximum absorption at lambda=426 nm with complex in acidic solution, using p-dimethylaminozenzaldehyde as color reagent, and the absorbance exhibits a linear reponses to the urea concentration over the range of 7.5-210 microg x mL(-1). The method for determining the rate of controlled-release urea pervasion through membrane was realized through determining the content of urea in the liquor, the recovery efficiency of the method is 96.1%-103.9%.
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BACKGROUND: Gemcitabine is the first-line drug for nonsmall cell lung cancer, and 18F-fluorodeoxyglucose. (18F-FDG) and 18F-fluorothymidine. (18F-FLT) are positron emission tomography. (PET) imaging agents. The aim of this study was to explore the effect of gemcitabine on the uptake of 18F-FDG and 18F-FLT in A549 cells and the animal tumor model. MATERIALS AND METHODS: The inhibitory effects of gemcitabine on cell growth were determined by tetrazolium blue method, and uptake rates of 18F-FDG and 18F-FLT were determined under the same conditions. The adenocarcinoma-bearing nude mice before and after gemcitabine treatments were performed microPET imaging with 18F-FDG and 18F-FLT. Hematoxylin and eosin staining and immunohistochemical analysis of tumor specimens were conducted. RESULTS: After the administration of gemcitabine, positive correlations were observed between inhibition of 18F-FDG or 18F.FLT uptake and cell growth. (r = 0.957 or 0.981, P < 0.01). SUVmax values by 18F-FDG in the tumor, before and after administration of gemcitabine at the dose of 60 mmol/L, revealed an increase by. (35.83 ± 10.58) %. After administration of 120 mmol/L gemcitabine, the SUVmax values decreased by (12.37 ± 7.33) %. The SUVmax values by 18F-FLT at the dose of 60 mmol/L gemcitabine revealed a decrease by (56.47 ± 10.83) %. Pathological staining showed obvious vasodilation and invasion of lymphocytes and plasma cells at the dose of 60 mmol/L, and the expression of glucose transporter protein-1, Ki-67 and proliferating cell nuclear antigen in tumor cells were inhibited. CONCLUSION: 18F-FLT imaging can assess the proliferation of tumor cells and 18F-FDG imaging can reflect the changes of the tumor microenvironment after administration of gemcitabine.
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Adenocarcinoma/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Desoxicitidina/análogos & derivados , Fluorodesoxiglucosa F18/administración & dosificación , Neoplasias Pulmonares/tratamiento farmacológico , Células A549 , Adenocarcinoma/diagnóstico por imagen , Adenocarcinoma/patología , Adenocarcinoma del Pulmón , Animales , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Carcinoma de Pulmón de Células no Pequeñas/patología , Proliferación Celular/efectos de los fármacos , Desoxicitidina/administración & dosificación , Modelos Animales de Enfermedad , Fluorodesoxiglucosa F18/metabolismo , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Ratones , Tomografía de Emisión de Positrones , Radiofármacos/administración & dosificación , Radiofármacos/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto , GemcitabinaRESUMEN
In this work, we proposed a novel simple protocol for preparing 1-aminopyrene/graphene (ApG) hybrids for fabricating label-free electrochemical impedance genosensor. Graphene, with the structure of a single-atom-thick sheet of sp(2)-bonded carbon atoms, was anchored to 1-aminopyrene (1-Ap) with the pyrenyl group viaπ-stacking interaction. The morphology, conductivity, and interaction of ApG hybrids were characterized by transmission electron microscopy (TEM), cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), UV-visible (UV-vis) and fluorescence spectra. The amino-substituted oligonucleotide probe was conjugated to 1-Ap by the cross-linker glutaraldehyde. The DNA hybridization reaction of oligonucleotide probe with target DNA was monitored by EIS. Under optimum conditions, the proposed biosensor exhibited high sensitivity and a low detection limit for detecting the complementary oligonucleotide. The target oligonucleotide could be quantified in a wide range of 1.0 × 10(-12) to 1.0 × 10(-8) M with good linearity (R = 0.9900) and low detection limit of 4.5 × 10(-13) M (S/N = 3).
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ADN/análisis , Grafito/química , Oligonucleótidos/química , Pirenos/química , ADN/química , Hibridación de Ácido Nucleico/métodosRESUMEN
BACKGROUND: Fluorine-18-fluorodeoxyglucose ((18)F-FDG) positron emission tomography imaging can be used to assess the treatment efficacy of chemotherapy and prognosis. The aim of this study was to determine the uptake rate of (18)F-FDG in colon cancer HCT-116 cells, and to evaluate the treatment efficacy of chemotherapy, hyperthermia and thermo-chemotherapy through the uptake inhibition rate of (18)F-FDG. METHODS: The uptake rate of (18)F-FDG in HCT-116 cells was determined at various experimental conditions. The inhibition rate of cell growth, uptake rate of (18)F-FDG and uptake inhibition rate of (18)F-FDG in HCT-116 cells treated with 5-fluorouracil (5-FU) at various concentrations were determined. In HCT-116 cells subjected to chemotherapy (5-FU, 100 µg/ml), hyperthermia (43°C, 40 minutes) and thermo-chemotherapy for 24 hours, the inhibition rate of cell growth and uptake inhibition rate of (18)F-FDG were determined; early apoptosis, the morphology and ultrastructure of HCT-116 cells were examined; and the contents of glucose and lactate dehydrogenase (LDH) in the cell culture medium of HCT-116 cells were determined. One-way analysis of variance (ANOVA) and correlation analyses were conducted by using SPSS 16.0 software. RESULTS: The uptake rate of (18)F-FDG in HCT-116 cells was (44.25 ± 2.19)%. Under the condition of adding 5-FU at various concentrations for 24 hours, the uptake rate of (18)F-FDG was negatively correlated with 5-FU dosage (r = -0.879, P < 0.01); the inhibition rate of cell growth revealed a positive correlation with the uptake inhibition rate of (18)F-FDG (r = 0.831, P < 0.01). In HCT-116 cells subjected to hyperthermia, chemotherapy, and thermo-chemotherapy for 24 hours, the uptake inhibition rates of (18)F-FDG were (12.94 ± 2.80)%, (28.25 ± 4.59)%, and (21.60 ± 3.68)%, respectively. The early apoptotic rates of HCT-116 cells were (9.80 ± 0.16)%, (19.80 ± 2.40)%, and (15.70 ± 1.80)%, respectively. Moreover, the contents of glucose and LDH in cell culture medium of HCT-116 cells after treatments were higher than those before treatment. CONCLUSION: The uptake inhibition rate of (18)F-FDG can be used for early evaluation of hyperthermia and 5-FU treatment efficacy on cancer cells although hyperthermia (43°C, 40 minutes) does not reveal the synergistic effect on 5-FU at the low dosage.