RESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Globally, the incidence rate and number of patients with nonalcoholic fatty liver disease are increasing, which has become one of the greatest threats to human health. However, there is still no effective therapy and medicine so far. Silphium perfoliatum L. is a perennial herb native to North America, which is used to improve physical fitness and treat liver and spleen related diseases in the traditional medicinal herbs of Indian tribes. This herb is rich in chlorogenic acids, which have the functions of reducing blood lipids, losing weight and protecting liver. However, the effect of these compounds on nonalcoholic fatty liver disease remains unclear. AIM OF THE STUDY: Clarify the therapeutic effects and mechanism of the extract (CY-10) rich in chlorogenic acid and its analogues from Silphium perfoliatum L. on non-alcoholic fatty liver disease, and to determine the active compounds. MATERIALS AND METHODS: A free fatty acid-induced steatosis model of HepG2 cells was established to evaluate the in vitro activity of CY-10 in promoting lipid metabolism. Further, a high-fat diet-induced NAFLD model in C57BL/6 mice was established to detect the effects of CY-10 on various physiological and biochemical indexes in mice, and to elucidate the in vivo effects of the extract on regulating lipid metabolism, anti-inflammation and hepatoprotection, and nontarget lipid metabolomics was performed to analyze differential metabolites of fatty acids in the liver. Subsequently, western blotting and immunohistochemistry were used to analyze the target of the extract and elucidate its mechanism of action. Finally, the active compounds in CY-10 were elucidated through in vitro activity screening. RESULTS: The results indicated that CY-10 significantly attenuated lipid droplet deposition in HepG2 cells. The results of in vivo experiments showed that CY-10 significantly reduce HFD-induced mouse body weight and organ index, improve biochemical indexes, oxidation levels and inflammatory responses in the liver and serum, thereby protecting the liver tissue. It can promote the metabolism of unsaturated fatty acids in the liver and reduce the generation of saturated fatty acids. Furthermore, it is clarified that CY-10 can promote lipid metabolism balance by regulating AMPK/FXR/SREPB-1c/PPAR-γ signal pathway. Ultimately, the main active compound was proved to be cryptochlorogenic acid, which has a strong promoting effect on the metabolism of fatty acids in cells. Impressively, the activities of CY-10 and cryptochlorogenic acid were stronger than simvastatin in vitro and in vivo. CONCLUSION: For the first time, it is clarified that the extract rich in chlorogenic acids and its analogues in Silphium perfoliatum L. have good therapeutic effects on non-alcoholic fatty liver disease. It is confirmed that cryptochlorogenic acid is the main active compound and has good potential for medicine.
Asunto(s)
Enfermedad del Hígado Graso no Alcohólico , Humanos , Animales , Ratones , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Proteínas Quinasas Activadas por AMP/metabolismo , Ratones Endogámicos C57BL , Hígado , Metabolismo de los Lípidos , Ácidos Grasos/metabolismo , Transducción de Señal , Dieta Alta en GrasaRESUMEN
Nitraria roborowskii Kom (NRK), with high economic and ecological value, is mainly distributed in the Qaidam Basin, China. However, research on its chemical components and bioactivities is still rare. In this study, its chemical constituents (52) including 10 ß-carboline alkaloids, nine cyclic peptides, three indole alkaloids, five pyrrole alkaloids, eight phenolic acids and 17 flavonoids were identified tentatively using UPLC-triple-TOF-MS/MS. Notablely, one new ß-carboline alkaloid and five new cyclic peptides were confirmed using MS/MS fragmentation pathways. In addition, experiments in vitro indicated that NRK-C had strong maltase and sucrase inhibitory activities (IC50 of 0.202 and 0.103 mg/mL, respectively). Polysaccharide tolerance experiments confirmed NRK-C (400 mg/kg) was associated with decreased postprandial blood glucose (PBG) in diabetic mice. These results suggested that NRK fruit might be used as a functional ingredient in food products.
Asunto(s)
Alcaloides , Diabetes Mellitus Experimental , Medicamentos Herbarios Chinos , Ratones , Animales , Espectrometría de Masas en Tándem , Cromatografía Líquida de Alta Presión/métodos , Extractos Vegetales/química , alfa-Glucosidasas/análisis , Frutas/química , Sacarasa , Alcaloides/análisis , Fenoles/análisis , Carbolinas/análisis , Péptidos Cíclicos/análisis , Medicamentos Herbarios Chinos/análisisRESUMEN
The mild-natured and bitter-flavored traditional Chinese medicines (MB-TCMs) are an important class of TCMs that have been widely used in clinical practice and recognized as safe long-term treatments for chronic diseases. However, as an important class of TCMs, the panorama of pharmacological effects and the mechanisms of MB-TCMs have not been systemically reviewed. Compelling studies have shown that gut microbiota can mediate the therapeutic activity of TCMs and help to elucidate the core principles of TCM medicinal theory. In this systematic review, we found that MB-TCMs commonly participated in the modulation of metabolic syndrome, intestinal inflammation, nervous system disease and cardiovascular system disease in association with promoting the growth of beneficial bacteria Bacteroides, Akkermansia, Lactobacillus, Bifidobacterium, Roseburia as well as inhibiting the proliferation of harmful bacteria Helicobacter, Enterococcus, Desulfovibrio and Escherichia-Shigella. These alterations, correspondingly, enhance the generation of protective metabolites, mainly including short-chain fatty acids (SCFAs), bile acid (BAs), 5-hydroxytryptamine (5-HT), indole and gamma-aminobutyric acid (GABA), and inhibit the generation of harmful metabolites, such as proinflammatory factors trimethylamine oxide (TAMO) and lipopolysaccharide (LPS), to further exert multiplicative effects for the maintenance of human health through several different signaling pathways. Altogether, this present review has attempted to comprehensively summarize the relationship between MB-TCMs and gut microbiota by establishing the TCMs-gut microbiota-metabolite-signaling pathway-diseases axis, which may provide new insight into the study of TCM medicinal theories and their clinical applications.
RESUMEN
Objective: Gut microbiome is an intricate micro-ecosystem mediating the human health and drug efficacy. Physalis alkekengi (PAL) is an edible and time-honored traditional Chinese medicine. Several pharmacological effects of PAL have been verified and gut bacteria are implied in its therapeutic actions. However, the detailed modulation of PAL on gut bacterial species and on gut fungi remains largely unknown. We, therefore, designed a preliminary experiment in normal mice to reveal the modulation effect of PAL on both gut bacteria and fungi, and explore the interaction between them. Methods: Herein, the aqueous extract of PAL was orally administrated to normal C57BL/6 mice for four weeks. The full-length 16S rRNA and ITS1/2 gene sequencing were explored to detect the taxa of gut bacteria and gut fungi after PAL treatment, respectively. Results: Oral administration of PAL notably enriched anti-inflammatory bacterial species such as Duncaniella spp. and Kineothrix alysoides, whereas decreased pro-inflammatory species such as Mucispirillum schaedleri. Simultaneously, PAL increased the abundance of gut fungi Aspergillus ochraceus, Cladosporium sp. and Alternaria sp., and decreased Penicillium janthinellum. Correlation network analysis identified two co-existing microbial groups (groups 1 and 2) that were negatively associated with each other. The group 1 comprised PAL-enriched bacteria and fungi, while group 2 was mainly normal chow-enriched bacteria and fungi. In group 1, Antrodia monomitica, Aspergillus clavatus, Mortierella kuhlmanii and Sarcinomyces sp. MA 4787 were positively correlated with Bifidobacterium globosum, Romboutsia ilealis and so on. In group 2, Chaetomium subspirilliferum, Septoria orchidearum and Cephaliophora tropica were positively related to Lactobacillus spp. Conclusion: Altogether, this preliminary study first demonstrated the modulation effect of PAL on both gut bacteria and gut fungi, which may shed light on the elucidation of PAL's pharmacological mechanism.
RESUMEN
A total of 18% of global breast cancer (BC) deaths are attributed to BC in China, making it one of the five most common cancers there. There has been a steady rise in BC morbidity and mortality in women in the last few years and it is now a leading cancer among Chinese women. Conventional treatments for BC are currently effective but have several limitations and disadvantages, and Traditional Chinese medicine (TCM) plays a vital role in the overall process of cancer prevention and therapy. It is known that TCM can treat a variety of conditions at a variety of sites and targets. In recent years, increasingly, research has been conducted on TCM's ability to treat BC. TCM has shown positive results in the treatment of breast cancer and the adverse effects of radiotherapy and chemotherapy. This review describes the progress of clinical observation and mechanism research of TCM in the treatment of breast cancer in recent years. It provides some ideas and theoretical basis for the treatment of BC with TCM.
RESUMEN
BACKGROUND: α-Glucosidase inhibitors could effectively reduce postprandial blood glucose (PBG) levels and control the occurrence of complications of diabetes. Gallotannins (GTs) in plants have attracted much attention due to their significant α-glucosidase inhibitory activities in vitro. However, there is still a lack of systematic comparative studies to further elucidate inhibitory activities in vivo and in vitro of these compounds against α-glucosidase, especially for mammalian sucrase and maltase, and analyze their structure-activity relationship. PURPOSE: Determine the in vitro and in vivo inhibitory activities of five GTs with different number of galloyl moieties (GMs) on sucrase, maltase and α-amylase, and elucidate the relationship between α-glucosidase inhibitory activities and the number and connection mode of GMs. METHODS: Molecular docking and dynamics were used to study the binding mode and binding ability of five GTs against sucrase, maltase and α-amylase. Then, the inhibitory activities and inhibitory mechanisms of these compounds on sucrase, maltase and α-amylase in vitro were studied using inhibitory assay and enzyme inhibition kinetics. Further, the hypoglycemic effects in vivo of these compounds were demonstrated by three polysaccharides tolerance experiments on diabetes model mice. RESULTS: The results of molecular docking showed that these compounds could bind to enzymes through hydrogen bonds, hydrophobic interactions, etc. In addition, the α-glucosidase inhibition comparative studies in vitro and in vivo demonstrated that the inhibitory activities of these compounds on all three sucrase, maltase and α-amylase were ranked as TA ≈ PGG > TeGG > TGG > 1GG, and their inhibitory activities increases with the increase in the number of GMs. Moreover, the hypoglycemic effects of 1,2,3,4,6-pentagalloylglucose (PGG) and tannic acid (TA) in vitro and in vivo were also confirmed to be equivalent to or even stronger than that of acarbose. CONCLUSION: α-Glucosidase inhibitory activities in vitro and in vivo of GTs were positively correlated with the number of GTs, and the more the number, the stronger the activity. However, PGG with five GTs and TA with ten GTs showed almost identical α-glucosidase inhibitory activities, possibly due to the reduced binding force with the enzyme caused by spatial hindrance.
Asunto(s)
alfa-Amilasas , alfa-Glucosidasas , Animales , Ratones , Taninos Hidrolizables/farmacología , Sacarasa , Simulación del Acoplamiento Molecular , Taninos , Inhibidores de Glicósido Hidrolasas/farmacología , MamíferosRESUMEN
Total petroleum hydrocarbon (TPH) contamination poses threats to ecological systems and human health. Many studies have reported its negative impacts on soil microbes, but limited information is known about microbial change and response to multiple TPH contamination events. In this study, we investigated TPH contamination level, microbial community structure and functional genes at a multi-contaminated industrial site in Lanzhou, where a benzene spill accident caused the drinking water crisis in 2014. TPHs distribution in soils and groundwater indicated multiple TPH contamination events in history, and identified the spill location where high TPH level (6549 mg kg-1) and high ratio of low-molecular-weight TPHs (>80%) were observed. In contrast, TPH level was moderate (349 mg kg-1) and the proportion of low-molecular-weight TPHs was 44% in soils with a long TPH contamination history. After the spill accident, soil bacterial communities became significant diverse (p = 0.047), but the dominant microbes remained the same as Pseudomonadaceae and Comamonadaceae. The abundance of hydrocarbon-degradation related genes increased by 10-1000 folds at the site where the spill accident occurred in multi-contaminated areas and was significantly related to 2-ring PAHs. Such changes of microbial community and hydrocarbon-degradation related genes together indicated the resilience of soil indigenous microbes toward multiple contamination events. Our results proved the significant change of bacterial community and huge shift of hydrocarbon-degradation related genes after the spill accident (multiple contamination events), and provided a deep insight into microbial response at industrial sites with a long period of contamination history.
Asunto(s)
Microbiota , Petróleo , Contaminantes del Suelo , Bacterias/genética , Bacterias/metabolismo , Biodegradación Ambiental , Humanos , Hidrocarburos/química , Petróleo/metabolismo , Suelo/química , Microbiología del Suelo , Contaminantes del Suelo/análisisRESUMEN
Codonopsis pilosula (Franch.) Nannf. (CPN), mainly planted in the northwest region, is a traditional Chinese medicine/good health food for nourishing qi and promoting blood circulation. This study firstly evaluated the inhibitory effects of the CPN extraction (CPNE) on α-glucosidase in vitro and in vivo, and tentatively confirmed its chemical ingredients by employing UHPLC-Triple-TOF-MS/MS. The CPNE had strong inhibitory activities against mammalian α-glucosidase (sucrase and maltase) and yeast α-glycosidase with semi-inhibitory concentrations (IC50) of 0.241 mg mL-1, 0.326 mg mL-1 and 1.167 mg mL-1, respectively. In addition, the CPNE could significantly decrease the postprandial blood glucose (PBG) levels in the sucrose/maltose/starch tolerance assays of diabetic mice. Furthermore, a total of 29 compounds, including 3 alkaloids, 13 phenolic acids, 8 alcohol glycosides and 5 alkynosides, were assigned based on comparison with the standards and references, as well as the analysis of main fragments. These results demonstrated that CPN could be used as an adjuvant therapy or dietary supplements to effectively control the occurrence and development of diabetes.
Asunto(s)
Codonopsis , Diabetes Mellitus Experimental/prevención & control , Medicamentos Herbarios Chinos/farmacología , Hipoglucemiantes/farmacología , Extractos Vegetales/farmacología , Aloxano , Animales , Animales no Consanguíneos , Cromatografía Líquida de Alta Presión , Medicamentos Herbarios Chinos/química , Glucosidasas/efectos de los fármacos , Hipoglucemiantes/química , Concentración 50 Inhibidora , Masculino , Ratones , Fitoterapia , Extractos Vegetales/química , Raíces de PlantasRESUMEN
Rhodiola crenulata (HK. f. et. Thoms) H. Ohba (RC), mainly distributed in the highly cold region of China, has long been used as a medicine/healthy food for eliminating fatigue and increasing blood circulation. This study aimed to evaluate the inhibitory effects of the RCRS extract on α-amylase and α-glucosidase (sucrase and maltase) in vitro and in vivo, and tentatively analyze and identify its chemical ingredients using UPLC-Triple-TOF/MS. The Rhodiola crenulata RCRS extract had strong inhibitory activities against α-amylase, sucrase and maltase with an IC50 of 0.031 mg mL-1, 0.142 mg mL-1 and 0.214 mg mL-1, respectively. Furthermore, the RCRS extract could significantly decrease the postprandial blood glucose (PBG) level of normal mice in a starch tolerance test, and reduce the PBG levels of diabetic mice in a starch/maltose/sucrose tolerance test. UHPLC-Triple-TOF-MS/MS analysis indicated that hydroxybenzoic acids, hydroxycinnamic acids, alcohol glycosides, flavonols and their derivatives were the main active ingredients in the RCRS extract. The results demonstrate that the RCRS extract of Rhodiola crenulata could be employed as a healthy food or medicine for controlling postprandial blood glucose levels.
Asunto(s)
Diabetes Mellitus Tipo 2/prevención & control , Hipoglucemiantes/farmacología , Extractos Vegetales/farmacología , Rhodiola , Animales , Animales no Consanguíneos , Glucemia , Cromatografía Líquida de Alta Presión , Modelos Animales de Enfermedad , Hipoglucemiantes/química , Masculino , Ratones , Extractos Vegetales/química , Raíces de Plantas , Ratas , Ratas Sprague-Dawley , Espectrometría de Masas en TándemRESUMEN
BACKGROUND: Improving potato productivity and quality plays an important role in enhancing global food security and human health. However, inappropriate fertilizer management negatively affects potato growth and tuber development, especially in developing countries where there are large numbers of smallholders without modern soil testing equipment. Nutrient Expert (NE), a new and convenient fertilization decision system, was evaluated in the present study by conducting four site-years field experiments in Northeast China, aiming to determine its effectiveness and applicability for potato production relative to local farmers' practice (FP) and fertilizer recommendation based on soil testing (ST). RESULTS: The excessive fertilization at planting promoted seedling growth for potato plants in FP. Nevertheless, superior plant growth and tuber development were observed in NE at the middle and later growing stages, by optimizing fertilizer input and implementing split fertilization. Overall, compared to FP, the NE system increased total and marketable tuber yields by 12-15% and 16-26%, respectively, at the same time as obtaining 19-31% higher net returns and enhanced fertilizer use efficiencies. Moreover, NE improved tuber quality by increasing the contents of starch, soluble protein and vitamin C and decreasing reducing sugar content relative to FP, as well as increasing starch yields by 23-52%. The ST method also showed comprehensive improvements in potato performances compared to FP, although it did not show any advantages compared to NE system. CONCLUSION: The NE system improved potato productivity and tuber quality by optimizing fertilization management, which is an effective and promising alternative to the ST method for potato production in China and other developing countries. © 2021 Society of Chemical Industry.
Asunto(s)
Fertilizantes/análisis , Nutrientes/metabolismo , Tubérculos de la Planta/química , Tubérculos de la Planta/crecimiento & desarrollo , Solanum tuberosum/metabolismo , Agricultura , China , Sistemas Especialistas , Calidad de los Alimentos , Nitrógeno/metabolismo , Tubérculos de la Planta/metabolismo , Suelo/química , Solanum tuberosum/química , Solanum tuberosum/crecimiento & desarrollo , Almidón/metabolismoRESUMEN
Cancer vaccines based on DNA encoding oncogenes have shown great potential in preclinical studies. However, the efficacy of DNA vaccines is limited by their weak immunogenicity because of low cellular internalisation and insufficient activation of dendritic cells (DCs). Calcium phosphate (CP) nanoparticles (NPs) are biodegradable vehicles with low toxicity and high loading capacity of DNA but suffer from stability issues. Here we employed adenosine triphosphate (ATP) as a dual functional agent, i.e. stabiliser for CP and immunological adjuvant, and applied the ATP-modified CP (ACP) NPs to the DNA vaccine. ACP NP-enhanced cellular uptake and improved transfection efficiency of DNA vaccine, and further showed the ability to activate DCs that are critical for them to prime T cells in cancer immunotherapy. As a result, a higher level of antigen-specific antibody with stronger tumour growth inhibition was achieved in mice immunised with the ACP-DNA vaccine. Overall, this one-step synthesised ACP NPs are an efficient nano-delivery system and nano-adjuvant for cancer DNA vaccines.
Asunto(s)
Adenosina Trifosfato/química , Adyuvantes Inmunológicos/química , Fosfatos de Calcio/química , Nanopartículas/química , Vacunas de ADN/química , Animales , Reacciones Antígeno-Anticuerpo , Vacunas contra el Cáncer/administración & dosificación , Vacunas contra el Cáncer/química , Vacunas contra el Cáncer/inmunología , Línea Celular Tumoral , Células Dendríticas/citología , Células Dendríticas/efectos de los fármacos , Células Dendríticas/inmunología , Inmunoterapia , Ratones , Ratones Endogámicos C57BL , Neoplasias/terapia , Trasplante Homólogo , Vacunación , Vacunas de ADN/inmunología , Vacunas de ADN/farmacologíaRESUMEN
Nitraria tangutorum Bobr. (NTB), mainly distributed in the Qaidam Basin of Tibetan Plateau, have high economic, ecological and medicinal value. The chemical compositions in the NTB fruits were tentatively analyzed and characterized by applying UPLC-Q-TOF-MS/MS. Total 45 constituents, including 9 hydroxycinnamic acids derivatives, 12 flavonols, 4 flavonoids, 1 trolox derivative, 8 ß-carboline alkaloids, 4 tryptophan derivatives, and 7 other amino acid derivatives were identified by comparing with standard products, and analyzing their retention times, characteristic fragment ions and deprotonated molecule ions. The activity studies in vitro indicated that NTB-Z and NTB-C extracts had marked inhibitory effects against sucrase and maltase. Further sucrose/maltose/starch tolerance experiment demonstrated that both NTB-Z and NTB-C extracts at 400 mg/kg could markedly lower the postprandial blood glucose (PBG) level in diabetic animals. All these results indicated that the NTB fruits could be used as the functional health food or medicine for controlling postprandial blood glucose level.
Asunto(s)
Alcaloides , Frutas , Animales , Cromatografía Líquida de Alta Presión , Glucosidasas , Extractos Vegetales/farmacología , Espectrometría de Masas en TándemRESUMEN
Phytochemical investigation on the ethanol extract of the fruits of Nitraria tangutorum Bobr. led to the isolation of a new flavonol acylglycoside tangutoside (7) and six known ones including p-formylphenol (1), 3-formylindole (2), rutin (3), prionitisid B (4), quercitrin (5) and flazin (6). Among them, compounds 2, 4, and 5 were isolated from Nitraria tangutorum Bobr. for the first time. Their structures were identified by spectroscopic methods and by comparison with data reported in the references. The compounds 3, 4, 5, and 7 were demonstrated to possess strong DPPH radical scavenging ability with IC50 values of 31.45 µg/mL, 19.21 µg/mL, 59.30 µg/mL, and 44.54 µg/mL, respectively.
Asunto(s)
Frutas , Magnoliopsida , Antioxidantes , Flavonoles , Extractos VegetalesRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Lamiophlomisrotata (Benth.) Kudo. has been used to treat trauma bleeding, rheumatism, yellow water disease in traditional Chinese medicine. AIM: The aim of this work was to evaluate the anti-rheumatoid arthritis (RA) activities and underlying mechanisms of the total iridoid glucosides (TIG) from Lamiophlomisrotata (Benth.) Kudo. METHODS: The chemical constituents of TIG was analyzed by high-performance liquid chromatography (HPLC) with seven reference compounds (penstemonoside, chlorotuberside, shanzhiside methyl ester, phloyoside, 7-epliamalbide, phlorigidoside C and lamalbide). The anti-rheumatoid arthritis effects of TIG were investigated by arthritis indexes and paw swelling degrees, as well as histopathological and Micro-CT analysis in adjuvant-induced arthritis (AIA) rats. The impacts of TIG on the level of inflammatory cytokines (IL-1ß, TNF-α, IL-6, IFN-γ, IL-17 and IL-10), and the regulation of OPG/RANKL/NF-κB pathways were determined by the ELISA and western blot, respectively. RESULTS: TIG significantly reduced the arthritis indexes and paws swelling in AIA rats, attenuated the inflammation and bone destruction in joint tissues, reduced the generation of pro-inflammatory cytokines IL-1ß, TNF-α, IL-6, IFN-γ and IL-17, as well as increased the generation of anti-inflammatory cytokine IL-10 in serum. Moreover, TIG markedly inhibited the expression of p-IKK-α, p-IκB and p-p65, and decreased the ratio of OPG/RANKL in the synovial tissues. CONCLUSION: TIG possessed significant anti-RA activities on adjuvant-induced arthritis, which might be ascribed to the regulation of inflammatory cytokines IL-1ß, TNF-α, IL-6, IFN-γ IL-17 and IL-10, as well as inhibition of OPG/RANKL/NF-κB signaling pathways.
Asunto(s)
Antirreumáticos/farmacología , Artritis Experimental/tratamiento farmacológico , Artritis Reumatoide/tratamiento farmacológico , Glicósidos Iridoides/farmacología , Lamiaceae/química , Animales , Antirreumáticos/aislamiento & purificación , Artritis Experimental/fisiopatología , Artritis Reumatoide/fisiopatología , Citocinas/metabolismo , Femenino , Inflamación/tratamiento farmacológico , Inflamación/fisiopatología , Glicósidos Iridoides/aislamiento & purificación , FN-kappa B/metabolismo , Osteoprotegerina/metabolismo , Ligando RANK/metabolismo , Ratas , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacosRESUMEN
Drug resistance and immune escape of tumor cells severely compromise the treatment efficiency of hepatocellular carcinoma (HCC). Long noncoding RNA KCNQ1 overlapping transcript 1 (lncRNA KCNQ1OT1) has been shown to be involved in drug resistance in several cancers. The aim of the present study was to investigate the role of KCNQ1OT1 in sorafenib resistance and immune escape of HCC cells. Reverse transcriptionquantitative PCR analysis, western blotting and immunohistochemistry were performed to detect the expression of KCNQ1OT1, miR506 and programmed deathligand1 (PDL1). Cell Counting Kit8 assay, flow cytometry and Transwell assays were used to evaluate IC50 value, cell apoptosis and metastasis. ELISA was performed to detect the secretion of cytokines. Dualluciferase reporter assay was conducted to verify the targeting relationships between miR506 and KCNQ1OT1 or PDL1. KCNQ1OT1 and PDL1 were found to be upregulated and miR506 was downregulated in sorafenibresistant HCC tissues and cells. Furthermore, KCNQ1OT1 knockdown reduced the IC50 value of sorafenib, suppressed cell metastasis and promoted apoptosis in sorafenibresistant HCC cells. Moreover, KCNQ1OT1 knockdown changed the tumor microenvironment and Tcell apoptosis in a sorafenibresistant HCC/Tcell coculture model. In addition, it was demonstrated that KCNQ1OT1 functioned as a competing endogenous RNA of miR506 and increased PDL1 expression in sorafenibresistant HCC cells. miR506 inhibition abolished the effects of KCNQ1OT1 knockdown on sorafenib sensitivity, tumor growth, the tumor microenvironment and Tcell apoptosis. In conclusion, KCNQ1OT1 knockdown inhibited sorafenib resistance and PDL1mediated immune escape by sponging miR506 in sorafenibresistant HCC cells.
Asunto(s)
Antígeno B7-H1/metabolismo , Carcinoma Hepatocelular/genética , Resistencia a Antineoplásicos , Evasión Inmune , Neoplasias Hepáticas/genética , MicroARNs/metabolismo , Sorafenib/uso terapéutico , Apoptosis/efectos de los fármacos , Apoptosis/genética , Secuencia de Bases , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Movimiento Celular/genética , Citocinas/metabolismo , Regulación hacia Abajo/efectos de los fármacos , Regulación hacia Abajo/genética , Resistencia a Antineoplásicos/efectos de los fármacos , Resistencia a Antineoplásicos/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Evasión Inmune/efectos de los fármacos , Evasión Inmune/genética , MicroARNs/genética , Modelos Biológicos , Invasividad Neoplásica , Canales de Potasio con Entrada de Voltaje/metabolismo , Sorafenib/farmacología , Linfocitos T/efectos de los fármacos , Linfocitos T/metabolismo , Microambiente Tumoral/efectos de los fármacos , Regulación hacia Arriba/efectos de los fármacos , Regulación hacia Arriba/genéticaRESUMEN
We discovered two antibacterial bimetallic nanoparticles (AuRh and AuRu NPs), that possess antibacterial activities against multi-drug resistant (MDR) Gram-negative bacteria and can cure wound infections. None of the nanoparticles comprising just one of these metals elements shows any antibiotic activities.
Asunto(s)
Antibacterianos/uso terapéutico , Infecciones Bacterianas/tratamiento farmacológico , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Nanopartículas del Metal/uso terapéutico , Animales , Antibacterianos/química , Antibacterianos/toxicidad , Escherichia coli/efectos de los fármacos , Femenino , Oro/química , Oro/toxicidad , Células Endoteliales de la Vena Umbilical Humana , Humanos , Nanopartículas del Metal/química , Nanopartículas del Metal/toxicidad , Pruebas de Sensibilidad Microbiana , Ratas Sprague-Dawley , Rodio/química , Rodio/toxicidad , Rutenio/química , Rutenio/toxicidad , Staphylococcus aureus/efectos de los fármacosRESUMEN
This study investigated the effect of L-theanine on carcass traits, meat quality, muscle antioxidant capacity, and amino acid (AA) profiles of broilers. Three hundred 1-day-old Ross 308 male broilers were randomly allotted to five groups with six replicates. Birds were fed the basal diet or basal diet with 300, 600, 900, or 1,500 mg/kg L-theanine for 42 consecutive days. The results showed that L-theanine quadratically increased dressing percentage, eviscerated percentage, and leg muscle yield (p < .05). Meanwhile, drip loss, cooking loss, shear force, L*24h, and muscle lactate content decreased quadratically in response to dietary L-theanine supplementation (p < .05), while pH24h and muscle glycogen content were quadratically improved by L-theanine (p < .05). Notably, the contents of muscle malondialdehyde and protein carbonyl, and the activities of muscle total antioxidant capacity, catalase, and glutathione peroxidase decreased quadratically in response to dietary L-theanine supplementation (p < .05), suggesting that the oxidative stress level of muscle was decreased quadratically. Moreover, L-theanine quadratically increased the concentrations of most of muscle essential AA, nonessential AA, and flavor AA (p < .05). In conclusion, L-theanine can be used as a valuable feed additive to modulate carcass traits, meat quality, muscle antioxidant status, and AA profiles of boilers, and its optimum addition level is 600 mg/kg based on the present study.
Asunto(s)
Aminoácidos/metabolismo , Fenómenos Fisiológicos Nutricionales de los Animales , Antioxidantes/metabolismo , Pollos/metabolismo , Dieta/veterinaria , Suplementos Dietéticos , Calidad de los Alimentos , Glutamatos/administración & dosificación , Glutamatos/farmacología , Carne/análisis , Músculos/metabolismo , Aminoácidos/análisis , Animales , Antioxidantes/análisis , Glutatión Peroxidasa/análisis , Glutatión Peroxidasa/metabolismo , Glucógeno/análisis , Glucógeno/metabolismo , Ácido Láctico/análisis , Ácido Láctico/metabolismo , Malondialdehído/análisis , Malondialdehído/metabolismoRESUMEN
Waste concrete is a key component of construction and demolition (C&D) waste produced in billions of tons. Exploring new technology for recycling waste concrete has become a global concern. Meanwhile, phosphorus (P) removal from wastewater consumes lots of natural minerals, leading to a heavy burden on the environment. In this study, the cement paste powder (HCPP) was used to remove phosphorus from wastewater. The results indicate that both HCPP and thermally modified HCPP (MHCPP) are effective phosphorus removal materials, with a maximum P-binding capacity of 3.9-mg P/g HCPP and 31.2-mg P/g MHCPP, respectively. The phosphorus removal mechanism of HCPP and MHCPP was also proposed: (1) Ca2+ and OH- can release from the surface of the HCPP or MHCPP to wastewater, forming a high-alkaline and Ca-rich solution; (2) hydrolysis of phosphorus species in the high-alkaline solution environment creates HPO42- species; (3) the HPO42- combines with Ca2+ and H2O, resulting in the formation of brushite; (4) the brushite precipitated from wastewater and adhered on the surface of the HCPP or the MHCPP particles. The study provides a new and low-cost material for treatment of phosphorus wastewater. Further, the study also offers a new approach for reusing of waste concrete fines.
Asunto(s)
Fósforo , Aguas Residuales/análisis , Materiales de Construcción , Minerales , ReciclajeRESUMEN
This study aims to isolate the potential antiproliferative and cytotoxic compounds from ginkgo biloba sarcotestas (GBS) and investigates the underlying mechanism in human MDA-MB-231 and mouse 4T-1 triple-negative breast cancer cells. Our results showed that 2-Hydroxy-6-tridecylbenzoic acid was isolated by cytotoxicity-guided fractionation where different fractions were assessed using MTT assay against MDA-MB-231 and 4T-1 cells. Colony formation assay showed that 2-Hydroxy-6-tridecylbenzoic acid significantly inhibited cell proliferation. The inhibition was associated with the enhancement of cytochrome P450 (CYP) 1B1 expression in a dose- and time-dependent manner and no significant change of CYP1A1 expression by qPCR and Western blot assays in MDA-MB-231 and 4T-1 cells. The mechanism was further demonstrated by the activation of aryl hydrocarbon receptor (AhR) pathway with the upregulation of AhR, AhR nuclear translocator (ARNT) and AhR-dependent xenobiotic response elements (XRE) activity. These findings may have implications for development of anticancer agents containing 2-Hydroxy-6-tridecylbenzoic acid as functional additives.
Asunto(s)
Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Benzoatos/farmacología , Proliferación Celular/efectos de los fármacos , Ginkgo biloba/química , Extractos Vegetales/farmacología , Receptores de Hidrocarburo de Aril/metabolismo , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Animales , Translocador Nuclear del Receptor de Aril Hidrocarburo/metabolismo , Benzoatos/uso terapéutico , Línea Celular Tumoral , Citocromo P-450 CYP1A1/metabolismo , Citocromo P-450 CYP1B1/metabolismo , Femenino , Humanos , Ratones , Extractos Vegetales/uso terapéutico , Neoplasias de la Mama Triple Negativas/patologíaRESUMEN
BACKGROUND: l-Theanine has multiple beneficial biological activities. However, there is little information about the use of l-theanine in broiler production. Therefore, this study investigated the effect of l-theanine on growth performance, intestinal development and health, and the mRNA levels of intestinal peptide and amino acid (AA) transporters of broilers. RESULTS: Body weight and average daily gain were increased by l-theanine, whereas feed to gain ratio was decreased (quadratic, P < 0.05). Notably, the relative weight of duodenum, jejunum and ileum, villus height, villus height to crypt depth ratio, the jejunal activities of glutathione peroxidase, total antioxidant capacity, catalase and total superoxide dismutase were increased linearly and/or quadratically by l-theanine (P < 0.05), whereas crypt depth, serum d-lactic acid, and jejunal protein carbonyls and malondialdehyde content were decreased linearly and/or quadratically (P < 0.05). Moreover, l-theanine enhanced the jejunal mRNA levels of occludin, claudin-1, E-cadherin, zona occludens-1, di- and tripeptide transporter, excitatory AA transporter 3, Na+ -independent cationic AA transporter 1, Na+ -independent cationic and zwitterionic AA transporter, Na+ - and Cl- -dependent neutral and cationic AA transporter, Na+ -independent cationic and Na+ -dependent neutral AA transporter (y+LAT) 1, y+LAT2, Na+ -independent branched-chain and aromatic AA transporter, and heavy chain corresponding to the b°,+ transport system (linear and/or quadratic, P < 0.05). CONCLUSIONS: l-Theanine beneficially affected the growth performance of broilers by improving intestinal development and health, and the intestinal mRNA levels of AA and peptide transporters. Therefore, l-theanine has the potential to be a promising feed additive for broilers. © 2020 Society of Chemical Industry.