RESUMO
Tumour-associated macrophages (TAMs) abundantly infiltrate high-grade gliomas and orchestrate immune response, but their diversity in isocitrate dehydrogenase (IDH)-differential grade 4 gliomas remains largely unknown. This study aimed to dissect the transcriptional states, spatial distribution, and clinicopathological significance of distinct monocyte-derived TAM (Mo-TAM) and microglia-derived TAM (Mg-TAM) clusters across glioblastoma-IDH-wild type and astrocytoma-IDH-mutant-grade 4 (Astro-IDH-mut-G4). Single-cell RNA sequencing was performed on four cases of human glioblastoma and three cases of Astro-IDH-mut-G4. Cell clustering, single-cell regulatory network inference, and gene set enrichment analysis were performed to characterize the functional states of myeloid clusters. The spatial distribution of TAM subsets was determined in human glioma tissues using multiplex immunostaining. The prognostic value of different TAM-cluster specific gene sets was evaluated in the TCGA glioma cohort. Profiling and unbiased clustering of 24,227 myeloid cells from glioblastoma and Astro-IDH-mut-G4 identified nine myeloid cell clusters including monocytes, six Mo/Mg-TAM subsets, dendritic cells, and proliferative myeloid clusters. Different Mo/Mg-TAM clusters manifest functional and transcriptional diversity controlled by specific regulons. Multiplex immunostaining of subset-specific markers identified spatial enrichment of distinct TAM clusters at peri-vascular/necrotic areas in tumour parenchyma or at the tumour-brain interface. Glioblastoma harboured a substantially higher number of monocytes and Mo-TAM-inflammatory clusters, whereas Astro-IDH-mut-G4 had a higher proportion of TAM subsets mediating antigen presentation. Glioblastomas with a higher proportion of monocytes exhibited a mesenchymal signature, increased angiogenesis, and worse patient outcome. Our findings provide insight into myeloid cell diversity and its clinical relevance in IDH-differential grade 4 gliomas, and may serve as a resource for immunotherapy development. © 2022 The Pathological Society of Great Britain and Ireland.
Assuntos
Astrocitoma , Neoplasias Encefálicas , Glioblastoma , Glioma , Astrocitoma/genética , Astrocitoma/patologia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Glioblastoma/genética , Glioblastoma/patologia , Glioma/genética , Humanos , Isocitrato Desidrogenase/genética , Mutação , Macrófagos Associados a TumorRESUMO
The environmental pollution, evolution of resistance, and risks to human and aquatic animal health associated with pesticide application have attracted much attention globally. Herein, we tested the capacity of diallyl trisulfide (DAT) from garlic essential oil to control the destructive stored-product pest, Sitotroga cerealella. The effects of DAT on the total content of cuticular chitin and structure of adults S. cerealella were evaluated. This study was the first to investigate changes in chitin structure in adults due to exposure to DAT through Fourier-transform infrared spectroscopy, thermogravimetric analysis, X-ray diffraction, and differential scanning calorimetry. The results of these analyses revealed that the cuticular chitin content of pests decreased after DAT treatment. DAT treatment also reduced thermal stability and crystallinity of chitin. These findings indicate that DAT is a potent biopesticide that is active against the moth, and establishes the basis for its use as an IPM and alternative to chitin synthesis inhibitors.
Assuntos
Alho , Mariposas , Óleos Voláteis , Compostos Alílicos , Animais , Quitina , SulfetosRESUMO
Breast cancer is one of the leading causes for cancer-related death among women worldwide. Coptidis Rhizoma has antibacterial,anti-inflammatory,anti-tumor and other pharmacological activities,but whether exercise could synergistically promote the role of RC in the treatment of breast cancer has not been reported. In this experiment,the effects and mechanism of total alkaloids of Coptidis Rhizoma combined with exercise on the tumor growth of orthotopically transplanted 4 T1 breast cancer were systemically studied in mice. Balb/C mice transplanted with 4 T1 cells in situ were used as models. The total alkaloids of RC(145 mg·kg-1·d-1) alone or in combination with exercise(10 m·min-1,30 min/time,5 times/week) were given for 28 days,and then the changes in body weight and tumor volume,tumor weight,interleukin-1ß(IL-1ß),serum estradiol(E2) content,and expression levels of estrogen receptor α(ERα),cell cycle related proteins CDK4,CDK6,cyclin D1,CDK2,and cyclin E in tumor tissues. The results showed that total alkaloids of Coptidis Rhizoma could significantly inhibit the growth of 4 T1 breast cancer in mice(P< 0. 01),and exercise significantly promoted the anti-tumor activity of total alkaloids of Coptidis Rhizoma(P<0. 01),and reduced E2 and IL-1ß levels in mice. Western blot and flow cytometry showed that the total alkaloids of Coptidis Rhizoma combined with exercise could down-regulate the protein expression levels of ERα,CDK4,CDK6,cyclin D1,CDK2 and cyclin E in cancer cells,block the transformation of G1/S in 4 T1 cell cycle,and inhibit DNA synthesis in breast cancer cells. The total alkaloids of Coptidis Rhizoma combined with exercise showed synergistic effect in inhibition of tumor growth in mice with orthotopically transplanted 4 T1 breast cancer.
Assuntos
Alcaloides/farmacologia , Neoplasias da Mama/terapia , Ciclo Celular/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Condicionamento Físico Animal , Animais , Linhagem Celular Tumoral , Coptis chinensis , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Transplante de Neoplasias , RizomaRESUMO
This work was mainly studied the effects of the four alkaloids from Coptidis Rhizoma on the mouse peritoneal macrophages in vitro and preliminarily discussed the regulating mechanisms. The effect of alkaloids from Coptidis Rhizoma on the vitality of macrophages was measured by the MTT assay. The effect of alkaloids on the phagocytosis of macrophages was determined by neutral red trial and respiratory burst activity was tested by NBT. The expressions of respiratory-burst-associated genes influenced by alkaloids were detected by qRT-PCR. The conformation change of membrane protein in macrophages by the impact of alkaloids was studied by fluorospectro-photometer. Results showed that the four alkaloids from Coptidis Rhizoma could increase the phagocytosis of macrophages in different level and berberine had the best effect. Berberine, coptisine and palmatine had up-regulation effects on respiratory burst activity of mouse peritoneal macrophages stimulated by PMA and regulatory activity on the mRNA expression of PKC, p40phox or p47phox, whereas the epiberberine had no significant influence on respiratory burst. Moreover, alkaloids from Coptidis Rhizoma could change the conformation of membrane protein and the berberine showed the strongest activity. The results suggested that the four alkaloids from Coptidis Rhizoma might activate macrophages through changing the conformation of membrane protein of macrophages and then enhanced the phagocytosis and respiratory burst activity of macrophages. Furthermore, the regulatory mechanism of alkaloids on the respiratory burst activity of macrophages may be also related to the expression level of PKC, p40phox and p47phox.
Assuntos
Alcaloides/farmacologia , Coptis/química , Medicamentos de Ervas Chinesas/farmacologia , Macrófagos Peritoneais/efeitos dos fármacos , Animais , Células Cultivadas , Feminino , Expressão Gênica/efeitos dos fármacos , Camundongos , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Proteína Quinase C/genética , Proteína Quinase C/metabolismo , Rizoma/químicaRESUMO
To study the effect of cholesterol and 25-OH-cholesterol on cholesterol metabolism in HepG2 cells and the effect of coptisine (Cop) extracted from Coptidis Rhizoma (CR) in reducing and regulating cholesterol. In this study, TC, TG, LDL-c and HDL-c were measured by biochemical analysis; mRNA and protein expressions of LDLR, HMGCR and CYP7A1 were detected by qRT-PCR and Western blot. According to the results, cholesterol and 25-OH-cholesterol inducing could decrease in mRNA and protein expressions of LDLR and CYP7A1, so as to increase TC and LDL-c contents. However, Cop could up-regulate mRNA and protein expressions of LDLR and CYP7A1 and down-regulate that of HMGCR, so as to reduce TC and LDL-c levels. These findings suggested that Cop has potential pharmacological activity for reducing cholesterol, and may reduce cholesterol by regulating mRNA and protein expressions of key genes involved in cholesterol metabolism, such as LDLR, CYP7A1 and HMGCR. This study laid a firm theoretical foundation for developing new natural drugs with the cholesterol-lowering activity.
Assuntos
Berberina/análogos & derivados , Colesterol 7-alfa-Hidroxilase/genética , Colesterol/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Hidroximetilglutaril-CoA Redutases/genética , Receptores de LDL/genética , Berberina/farmacologia , Colesterol 7-alfa-Hidroxilase/metabolismo , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Humanos , Hidroximetilglutaril-CoA Redutases/metabolismo , Receptores de LDL/metabolismo , Triglicerídeos/metabolismoRESUMO
To investigate the practicability of establishing zebrafish lipid-lowering drug screening model and the effect of berberine (BBR) on hyperlipidemic zebrafish. Three-month-old zebrafishes were fed with 4% cholesterol for 0, 2, 4, 8, 14, 20, 25, 30 days, and the level of total cholesterol in serum was measured. Zebrafish were randomly divided into four groups: the control group, the high cholesterol diet group, the 0.01% simvastatin-treated group, the 0.1% berberine-treated group and the 0.2% berberine-treated group. The levels of total cholesterol (TC), triglyceride (TC), low density lipoprotein cholesterol (LDL-c) and high-density lipoprotein cholesterol (HDL-c) in serum were measured; the expression of hepatic HMGCR, LDLR and CYP7A1a mRNA expressions were detected by real time PCR. Oil red O staining was performed to observe the changes in fat content in the liver. According to the result, the level of serum TC in the 4% cholesterol diet group significantly was higher than that of the normal control group in a time-dependent manner and reached a stable level at the 20th day. The BBR group showed significant decreases in the levels of TC, TG and LDL-c, HMGCR mRNA expression and fat content and increases in LDLR and CYP7A1a mRNA. The hyperlipidemia zebrafish model was successfully established by feeding with 4% cholesterol for 20 days. The findings lay a foundation for further screenings on lipid-lowering drugs.
Assuntos
Berberina/administração & dosagem , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/administração & dosagem , Hiperlipidemias/tratamento farmacológico , Hipolipemiantes/administração & dosagem , Peixe-Zebra/metabolismo , Animais , Colesterol/metabolismo , Feminino , Humanos , Hiperlipidemias/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Triglicerídeos/metabolismoRESUMO
To explore the antibacterial activity and mechanism of total alkaloids and berberine from Coptidis Rhizoma on Aeromonas hydrophila, and determine the effect of total alkaloids and berberine from Coptidis Rhizoma on minimum inhibitory concentrations, permeability and fluidity of cell membrane, conformation of membrane proteins and virulence factors of A. hydrophila. The results showed that both total alkaloids and berberine from Coptidis Rhizoma had antibacterial activities on A. hydrophila, with minimum inhibitory concentrations of 62.5 and 125 mg · L(-1), respectively. Total alkaloids and berberine from Coptidis Rhizoma could increase the fluidity of membrane, change the conformation of membrane porteins and increase the permeability of bacteria membrane by 24.52% and 19.66%, respectively. Besides, total alkaloids and berberine from Coptidis Rhizoma significantly decreased the hemolysis of exotoxin and the mRNA expressions of aerA and hlyA (P < 0.05, P < 0.01), the secretion of endotoxin and the mRNA expression of LpxC (P < 0.05, P < 0.01). The results suggested that the antibacterial activity of total alkaloids and berberine from Coptidis Rhizoma on A. hydrophila may be related to the bacteria membrane injury. They inhibited the bacterial growth by increasing membrane lipid fluidity and changing conformation of membrane proteins, and reduced the secretion of virulence factors of A. hydrophila to weaken the pathogenicity.
Assuntos
Aeromonas hydrophila/efeitos dos fármacos , Alcaloides/farmacologia , Antibacterianos/farmacologia , Berberina/farmacologia , Membrana Celular/efeitos dos fármacos , Coptis/química , Medicamentos de Ervas Chinesas/farmacologia , Aeromonas hydrophila/genética , Aeromonas hydrophila/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Toxinas Bacterianas/biossíntese , Membrana Celular/genética , Membrana Celular/metabolismo , Fluidez de Membrana/efeitos dos fármacos , Rizoma/químicaRESUMO
The concentrations of berberine (BBR) and 8-cetylberberine (8-BBR-C16) in rat plasma and tissue were determined by RP-HPLC. Both the plasma pharmacokinetics characteristic and tissue distribution differences of BBR and 8-BBR-C16 were compared to provide experimental data for the mechanism research and further drug development. After the oral administrations of BBR and 8-BBR-C16 at the dose of 80 mg x kg(-1) for rats, the pharmacokinetics result showed that compared with BBR, the C(max) and AUC(0-t), of 8-BBR-C16 increased by 2.8 times and 12.9 times respectively, t1/2 extended from 3.61 h to 11.90 h. The tissue distribution result showed that compared with BBR, the concentration of 8-BBR-C16 in various organizations increased and the retention time extended remarkably. The maximum concentration was achieved in lung and the highest concentration in it was 3 731.82 ng x g(-1). After being derived, the C(max) in plasma and bioavailability of 8-BBR-C16 increased remarkably and the circulation time in vivo extended. The drug concentration in tissue increased remarkably, and the distribution ratio changed too, with strong targeting selection in lung.
Assuntos
Berberina/análogos & derivados , Berberina/farmacocinética , Administração Oral , Animais , Disponibilidade Biológica , Cromatografia Líquida de Alta Pressão , Ratos , Distribuição TecidualRESUMO
To study the effects of alkaloids from Coptidis Rhizoma on low-density lipoprotein receptor (LDLR) mRNA expression and antihyperlipedemic levels. The LDLR mRNA expression were detected by real time fluorescence quantitative PCR, and the levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL-c) and high-density lipoprotein cholesterol (HDL-c) in serum were measured at the first and last examination. The results show that, after the drug treatment, compared with the model group, each drug group showed a lipid-lowering effect. Especially, coptisine, palmatine, jatrorrhinze were significantly reduced TC, TG, LDL-c (P < 0.05, P < 0.01), and increased HDL-c (P < 0.01). In addition, they also increased mRNA expression of the LDLR in liver and HepG2 cells. The results showed that alkaloids from Coptidis Rhizoma can regulate lipid metabolism disorder, and coptisine have the best lipid-lowering effect.
Assuntos
Alcaloides/administração & dosagem , Medicamentos de Ervas Chinesas/administração & dosagem , Hiperlipidemias/tratamento farmacológico , Hiperlipidemias/metabolismo , Hipoglicemiantes/administração & dosagem , Metabolismo dos Lipídeos/efeitos dos fármacos , Receptores de Lipoproteínas/metabolismo , Animais , Colesterol/metabolismo , Coptis chinensis , Cricetinae , Humanos , Hiperlipidemias/genética , Lipídeos/sangue , Lipoproteínas LDL/metabolismo , Mesocricetus , Receptores de Lipoproteínas/genética , Triglicerídeos/metabolismoRESUMO
OBJECTIVE: To investigate the effect of different parts, harvesting time and processing technologies on alkaloids content of Coptis chinensis adventitious root. METHODS: The content of alkaloids were analyzed by HPLC. RESULTS: The content of total alkaloids in adventitious root harvested in different time was ranged from 2.5% to 2.9%, in which that of berberine and coptisine were the highest, reaching to 1%, and that of palmatine was only 0.1%. It suggested there was no significant difference of total alkaloids at different harvesting time. Nevertheless, the difference of the alkaloids content from different parts was much significant. The content of total alkaloid of adventitious root near to rhizome was about 4%, 2 times higher than that away from rhizome (only 2%). In addition, different processing technologies would affect alkaloids content obviously. There was hardly loss of alkaloids when the fresh adventitious root was washed with water, but it would decrease alkaloids content when the dried adventitious root was washed. CONCLUSION: Medicine value of Coptis chinensis adventitious root near to rhizome is higher than that away from rhizome. And fresh Coptis chinensis adventitious root can be washed with water.
Assuntos
Alcaloides/análise , Coptis/química , Composição de Medicamentos/métodos , Raízes de Plantas/química , Plantas Medicinais/química , Berberina/análogos & derivados , Berberina/análise , Cromatografia Líquida de Alta Pressão , Estações do Ano , Fatores de TempoRESUMO
Human activities emitting carbon dioxide (CO2) have caused severe greenhouse effects and accelerated climate change, making carbon neutrality urgent. Seawater mineral carbonation technology offers a promising negative emission strategy. This work investigates current advancements in proposed seawater mineral carbonation technologies, including CO2 storage and ocean chemical carbon sequestration. CO2 storage technology relies on indirect mineral carbonation to fix CO2, involving CO2 dissolution, Ca/Mg extraction, and carbonate precipitation, optimized by adding alkaline substances or using electrochemical methods. Ocean chemical carbon sequestration uses natural seawater for direct mineral carbonation, enhanced by adding specific materials to promote carbonate precipitation and increase CO2 absorption, thus enhancing marine carbon sinks. This study evaluates these technologies' advantages and challenges, including reaction rates, costs, and ecological impacts, and analyzes representative materials' carbon fixation potential. Literature indicates that seawater mineral carbonation can play a significant role in CO2 storage and enhancing marine carbon sinks in the coming decades.
Assuntos
Dióxido de Carbono , Sequestro de Carbono , Água do Mar , Água do Mar/química , Dióxido de Carbono/análise , Mudança Climática , Carbonatos/química , Minerais/químicaRESUMO
OBJECTIVE: To optimize the processing technology of Coptidis Rhizoma and study the effects of different adjuvants on alkaloids during processing. METHODS: The moistening time of adjuvants (A), processing temperature (B) and processing time (C) were investigated by using the single factor test method and L9 (3(4)) orthogonal experiment design with the contents of four alkaloids as indexes. RESULTS: The sequence of importance of the factors that affect the wine processed Coptidis Rhizoma (WC) was C > B > A, turmeric processed Coptidis Rhizoma (TC) and dogwood processed Coptidis Rhizoma (DC) was B > A > C. CONCLUSION: The optimal processing technology of WC, TC and DC are drying for 4 h at 130 degrees C after moistening for 90 min, drying for 3 h at 100 degrees C after moistening for 60 min and drying for 2 h at 160 degrees C after moistening for 90 min, respectively.
Assuntos
Alcaloides/análise , Coptis/química , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Tecnologia Farmacêutica/métodos , Berberina/análise , Cromatografia Líquida de Alta Pressão , Evodia/química , Excipientes/química , Frutas/química , Temperatura Alta , Rizoma/química , Fatores de Tempo , Vinho , Zingiberaceae/químicaRESUMO
Synthetic fluoroquinolones (FQs) are the third most commonly used antibiotics in the world and play an extremely important role in antibacterial drugs. The excessive use and discharge will alter ecological environment, with consequence on human health and global sustainable development. It is therefore of great significance for scientific use and management of FQs to systematically understand their biogeochemical behavior and eco-environmental effects. After drug administration in humans and animals, only a small part of FQs are transformed in vivo. The main transformation processes include formylation, acetylation, oxidation and cleavage of piperazine ring, defluorination and decarboxylation of aromatic core ring, etc. About 70% of the original drug and a small amount of transformed products would be migrated to the environment through excretion. After entering the environment, FQs and their transformation products mainly exist in environmental media such as water, soil and sediment, and undergo migration and transformation processes such as adsorption, photolysis and biodegradation. Adsorption facilitates transfer of FQs from medium to another. The photolysis mainly affects the C7-amine substituents of FQs, whereas the core structure of FQs remains intact. Biodegradation mainly refers to the degradation of FQs by microorganisms and microalgae, including piperazine modification of the piperazine ring such as acetylation and formylation, partial or complete ring cleavage, core structure decarboxylation, defluorination and conjugation formation. The migration and transformation processes of FQs cannot completely eliminate them from the environment. Instead, they would become "pseudo-persistent" pollutants, which seriously affect the behavior, growth and reproduction of algae, crustaceans and fish, change biogeochemical cycle, destroy aquatic environment, and stimulate microbial resistance and the generation of resistance genes. In the future, more in-depth studies should be conducted on the environmental behavior of FQs and their impacts on ecological environment, the risk assessment of microbial resistance and resistance genes of FQs, and the mechanism and effect of micro-biodegradation of FQs.
Assuntos
Clima , Fluoroquinolonas , Animais , Humanos , Antibacterianos , Biodegradação Ambiental , PiperazinasRESUMO
Fluoroquinolone antibiotics (FQs) are one of the most widely used antibiotics, which are new pollutants with 'pseudo persistence' in the environment, causing great ecological risks. FQs could change the structure and function of microbial communities and affect nitrogen cycling mediated by microorganisms. Consequently, FQs would change the composition of various types of nitrogen in the environment and exert a significant impact on the global nitrogen cycling. We encapsulated the distribution of FQs in the environment and its impacts on nitrogen cycling mediated by microorganisms, explained the role of FQs in each key process of nitrogen cycling, aiming to provide an important reference for revealing the ecological effects of FQs. Generally, FQs could be detected in various environmental media, with significant differences in the concentration and types of FQs in different environments. Ofloxacin, norfloxacin, ciprofloxacin, and enrofloxacin are the four types of FQs with the highest detection frequency and concentration. The effect of FQs on nitrogen cycling deeply depends on typical characteristics of concentration and species. FQs mainly inhibit nitrification by reducing the abundance of amoA gene related to ammoxidation process and the abundance and composition of ammoxidation bacteria. FQs inhibits nitrification by reducing the abundance and composition of microbial communities. The denitrification process is mainly inhibited due to the reduction of the activity of related enzymes and the abundance of genes such as narG, nirS, norB, and nosZ genes, as well as the abundance and composition of denitrifying functional microorganisms. The process of anammox is restricted due to the reduction of the abundance, composition and hzo gene abundance of anaerobic anammox bacteria. FQs lead to the reduction of active nitrogen removal and the increase of N2O release in the environment, with further environmental problems such as water eutrophication and greenhouse effect. In the future, we should pay attention to the effects of low concentration FQs and complex antibiotics on the nitrogen cycling, and focus on the effects of FQs on the changes of nitrogen cycle-related microbial monomers and communities.
Assuntos
Fluoroquinolonas , Ciclo do Nitrogênio , Fluoroquinolonas/química , Antibacterianos/farmacologia , Antibacterianos/química , Poluição Ambiental , Nitrogênio , DesnitrificaçãoRESUMO
Epiberberine (EPI), extracted from Rhizome Coptidis, has been shown to attenuate hyperlipidemia in vivo. Herein we have studied the mechanism by which EPI is active against non-alcoholic steatohepatitis (NASH) using, mice fed on a methionine- and choline-deficient (MCD) diet and HepG2 cells exposed to free fatty acids (FFA). We show that small heterodimer partner (SHP) protein is key in the regulation of lipid synthesis. In HepG2 cells and in the livers of MCD-fed mice, EPI elevated SHP levels, and this was accompanied by a reduction in sterol regulatory element-binding protein-1c (SREBP-1c) and FASN. Therefore, EPI reduced triglyceride (TG) accumulation in steatotic hepatocytes, even in HepG2 cells treated with siRNA-SHP, and also improved microbiota. Thus, EPI suppresses hepatic TG synthesis and ameliorates liver steatosis by upregulating SHP and inhibiting the SREBP1/FASN pathway, and improves gut microbiome.
Assuntos
Berberina , Hepatopatia Gordurosa não Alcoólica , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , LipídeosRESUMO
Sulfonamides (SAs) are the first broad-spectrum synthetic antimicrobial agents used in human health and veterinary medicine. The majority of SAs entering human body is discharged into aquatic environment in the form of parent material or metabolites. The residues of SAs and their metabolites in the aquatic environment and the development of drug resistance can be serious threats to ecosystems and human health. We summarized recent advances in the research of SAs. The main metabolite types of SAs and the distribution characteristics of metabolites in different aquatic environments were introduced. The ecotoxicology of SAs metabolites, especially the distribution and hazards of sulfonamide resistance genes (sul-ARGs), were discussed with emphasis. Finally, the future research works were proposed. This paper could provide basic information for further research on SAs.
Assuntos
Ecossistema , Ecotoxicologia , Humanos , Sulfanilamida , Sulfonamidas/toxicidadeRESUMO
OBJECTIVE: To extract lectins from Trichosanthes kirilowi and study their hypoglycemic activity. METHODS: The optimal extraction process included the following parameters were conformed by optimization analysis,lectins extracted from Trichosanthes kirilowi was achieved by ammonium sulfate precipitation; The agglutinate activity was determined by using the agglutination test with 5% human blood cells. Human hepatocarcinoma cell HepG2 and the alloxan-induced diabetic mice model were used to assess hypoglycemic activity of Lectin in Trichosanthes kirilowi. RESULTS: The agglutination indexes of lectins extraction buffer were 32; The cell and mice tests indicated that the lectins exhibited hypoglycemic activity in the 70% saturation. CONCLUSION: The optimum extraction technology is as follows: extraction with PBS, the material-water ratio is 1:30, the extraction time is 24 h, while the concentration of sodium chloride is 0 mol/L and pH is 7.2. Precipitate lectins by ammonium sulfate in the 70% saturation, centrifugal speed is 10 000 tracted from Trichosanthes kirilowi exposes proper hypoglycemic activity.
Assuntos
Diabetes Mellitus Experimental/patologia , Hipoglicemiantes/farmacologia , Lectinas de Plantas/isolamento & purificação , Lectinas de Plantas/farmacologia , Trichosanthes/química , Sulfato de Amônio/química , Animais , Glicemia/metabolismo , Diabetes Mellitus Experimental/sangue , Hemaglutinação/efeitos dos fármacos , Testes de Hemaglutinação , Células Hep G2 , Humanos , Concentração de Íons de Hidrogênio , Hipoglicemiantes/isolamento & purificação , Masculino , Camundongos , Camundongos Endogâmicos , Lectinas de Plantas/química , Raízes de Plantas/química , Tecnologia Farmacêutica/métodos , Fatores de TempoRESUMO
A plug-and-play surface plasmon resonance (SPR) dual-parameter optical fiber biosensor is reported, in which Au film was firstly coated on the fiber surface for exciting SPR and the end half of the Au film was modified with Au nanoparticles to generate double SPR resonance valleys. For simultaneous detecting of glucose and cholesterol concentrations, modified P-mercaptophenylboronic acid (PMBA) and ß-cyclodextrin (ß-CD) were subsequently coated on the surface of sensor probe. Due to the cis-diol structure of glucose, it can interact with PMBA, leading to a red shift of one SPR resonant valley, whose maximum wavelength shift is 11.228 nm in the range of 0-1.7 mM glucose concentration. On the same time, the cholesterol molecules can realize the host-guest combination with ß-CD, leading to a red shift of another SPR resonant valley, and the maximum wavelength shift is 18.893 nm in the cholesterol concentration range of 0-300 nM. The detection limits of the sensor to glucose and cholesterol are 0.00078 mM and 0.012 nM, respectively. The enhances the practical value of the dual-parameter sensor. Both theory and experiment results verify the feasibility of the "plug-and-play" sensor to measure the dual biomass of glucose and cholesterol with ultra-low detection limit and good selectivity. The proposed method provides a huge research value for the optical fiber sensor in multi-parameter measurement.
Assuntos
Técnicas Biossensoriais , Nanopartículas Metálicas , Colesterol , Tecnologia de Fibra Óptica , Glucose , Ouro , Fibras Ópticas , Ressonância de Plasmônio de SuperfícieRESUMO
BACKGROUND AND PURPOSE: Zuojin capsule (ZJC), a classical prescription, is outstanding in improving the conditions of patients with gastrointestinal diseases and colorectal cancer (CRC). Although ZJC has multi-ingredient and multi-target characteristics, its pharmacological effect on colorectal cancer and the underlying mechanism remain unclear. METHOD: Here, the activity of ZJC against CRC was evaluated by the experiments with CRC cells and HCT-116 xenografted mice. The key genes of CRC were obtained from the cancer genome atlas (TCGA). The genes potentially targeted by ZJC were collected from traditional Chinese medicine systems pharmacology (TCMSP) database. The underlying pathways related to selected targets were analyzed through gene ontology (GO) and pathway enrichment analyses. Western blot (WB), cellular thermal shift assay (CETSA), molecular docking and quantitative real-time PCR (QRT-PCR) were carried out to confirm the validity of the targets. RESULTS: In vitro and in vivo results indicated that ZJC may inhibit CRC cells and tumor growth. The network pharmacological analysis indicated that 22 compounds, 51 targets and 20 pathways were involved in the compound-target-pathway network. Our results confirmed that ZJC inhibited cycle progression, migration and induced apoptosis by targeting candidate genes (CDKN1A, Bcl2, E2F1, PRKCB, MYC, CDK2, and MMP9). We found that ZJC could directly change the protein level by regulating the protein stability and transcriptional activity of the target. CONCLUSIONS: In summary, combined network pharmacology and biological experiments proved that the main ingredients of ZJC such as quercetin, (R)-Canadine, palmatine, rutaecarpine, evodiamine, beta-sitosterol and berberine can target CDKN1A, Bcl2, E2F1, PRKCB, MYC, CDK2 and MMP9 to combat colorectal cancer. The results of this study provide a basic theory for the clinical trials of Zuojin Capsules against colorectal cancer.
Assuntos
Neoplasias Colorretais , Medicamentos de Ervas Chinesas , Animais , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Medicina Tradicional Chinesa , Camundongos , Simulação de Acoplamento Molecular , Farmacologia em RedeRESUMO
Antimony is a naturally occurring and cumulatively toxic element. With increasing concern as an inorganic contaminant, research on its environmental behavior is becoming a necessity. However, very little is known about this element. To further understand its biogeochemical behaviors and roles in the ecosystem, the main species of dissolved inorganic antimony (Sb(iii) and Sb(v)) in Yangtze River Estuary and its adjacent waters were determined by hydride generation and atomic fluorescence (HG-AFS) in our study. Results show that in surface water, the concentration for Sb(iii) and Sb(v) were in the range 0.029 µg L(-1)â¼ 0.736 µg L(-1) and 0.121 µg L(-1)â¼ 2.567 µg L(-1), with averages of 0.152 µg L(-1) and 0.592 µg L(-1), respectively. While concentrations of Sb(iii) and Sb(v) in the bottom layer were much lower, ranging from 0.023 µg L(-1) to 0.116 µg L(-1) (average of 0.050 µg L(-1)) and from 0.047 µg L(-1) to 0.441 µg L(-1) (average of 0.194 µg L(-1)), respectively. Data analysis further demonstrates that the major processes controlling antimony geochemistry in the area are riverine input, atmospheric deposition, incursion of Taiwan Warm Current, and release from particulate phase. The surface-enrichment and bottom-depletion depth profile reveals it does appear as a mildly scavenged element but is less like arsenic than previously believed. Sb(v) was the predominant speciation in aquatic environment of our research, and Sb(iii) was a minor constituent of the total antimony. Regarding the adsorption-desorption process onto SPM, Sb(iii) has a higher affinity to particulate phase than Sb(v). Furthermore, the significant correlation between antimony and nutrients indicates it is an element with great biological potential, which is also an important behavior for antimony.