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Background: Polycystic ovary syndrome (PCOS), a common endocrine and reproductive disorder, lacks precise diagnostic strategies. Necroptosis was found to be crucial in reproductive and endocrine disorders, but its function in PCOS remains unclear. We aimed to identify differentially diagnostic genes for necroptosis (NDDGs), construct a diagnostic model to assess the progression of PCOS and explore the potential therapeutic drugs. Methods: Gene expression datasets were combined with weighted gene co-expression network analysis (WGCNA) and necroptosis gene sets to screen the differentially expressed genes for PCOS. Least absolute shrinkage and selection operator (LASSO) regression analysis was used to construct a necroptosis-related gene signatures. Independent risk analyses were performed using nomograms. Pathway enrichment of NDDGs was conducted with the GeneMANIA database and gene set enrichment analysis (GSEA). Immune microenvironment analysis was estimated based on ssGSEA algorithm analysis. The Comparative Toxicogenomics Database (CTD) was used to explore potential therapeutic drugs for NDDGs. The expression of NDDGs was validated in GSE84958, mouse model and clinical samples. Results: Four necroptosis-related signature genes, IL33, TNFSF10, BCL2 and PYGM, were identified to define necroptosis for PCOS. The areas under curve (AUC) of receiver operating characteristic curve (ROC) for training set and validation in diagnostic risk model were 0.940 and 0.788, respectively. Enrichment analysis showed that NDDGs were enriched in immune-related signaling pathways such as B cells, T cells, and natural killer cells. Immune microenvironment analysis revealed that NDDGs were significantly correlated with 13 markedly different immune cells. A nomogram was constructed based on features that would benefit patients clinically. Several compounds, such as resveratrol, tretinoin, quercetin, curcumin, etc., were mined as therapeutic drugs for PCOS. The expression of the NDDGs in the validated set, animal model and clinical samples was consistent with the results of the training sets. Conclusion: In this study, 4 NDDGs were identified to be highly effective in assessing the progression and prognosis of PCOS and exploring potential targets for PCOS treatment.
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Síndrome del Ovario Poliquístico , Animales , Ratones , Femenino , Humanos , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Síndrome del Ovario Poliquístico/genética , Necroptosis/genética , Algoritmos , Área Bajo la Curva , Linfocitos B , Microambiente TumoralRESUMEN
Our previous research discovered that combining the PDA-PEG polymer with copper ions can selectively kill cancer cells. However, the precise mechanism by which this combination functions was not fully understood. This study revealed that the PDA-PEG polymer and copper ions form complementary PDA-PEG/copper (Poly/Cu) nanocomplexes by facilitating copper ion uptake and lysosomal escape. An in vitro study found that Poly/Cu killed 4T1 cells through a lysosome cell death pathway. Furthermore, Poly/Cu inhibited both the proteasome function and autophagy pathway and induced immunogenic cell death (ICD) in 4T1 cells. The Poly/Cu induced ICD coupled with the checkpoint blockade effect of the anti-PD-L1 antibody (aPD-L1) synergistically promoted immune cell penetration into the tumor mass. Benefiting from the tumor-targeting effect and cancer cell-selective killing effect of Poly/Cu complexes, the combinatory treatment of aPD-L1 and Poly/Cu effectively suppressed the progression of triple-negative breast cancer without inducing systemic side effects.
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Polímeros , Neoplasias de la Mama Triple Negativas , Humanos , Polímeros/uso terapéutico , Cobre/farmacología , Cobre/uso terapéutico , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Inmunoterapia , Lisosomas , Muerte Celular , Linfocitos , Línea Celular TumoralRESUMEN
BACKGROUND: Recovery of high-purity tea saponin (TS), a promising non-ionic surfactant with well-documented properties, is one of the major challenges to broadening its industrial applications. In this study, an innovative and sustainable strategy for the highly-efficient purification of TS was developed by using well-designed highly-porous polymeric adsorbents. RESULTS: The prepared Pp-A with controllable macropores (~96 nm) and appropriate surface hydrophobic properties was found more favorable for achieving high adsorption efficiency towards TS/TS-micelles. Kinetic results showed the adsorption follows the pseudo-second-order model (R2 = 0.9800), and the Langmuir model is more qualified to explicate the adsorption isotherms with Qe-TS ~ 675 mg g-1 . Thermodynamic studies revealed the monolayer adsorption of TS was an endothermic process that was conducted spontaneously. Interestingly, ethanol-driven desorption (90% v/v ethanol) of TS was rapidly (< 30 min) complete due to the possible ethanol-mediated disassembling of TS-micelles. A possible mechanism that involves the interactions between the adsorbents and TS/TS-micelles, the formation and disassembling of TS-micelles was proposed to account for the highly efficient purification of TS. Afterwards, Pp-A-based adsorption method was developed to purify TS directly from industrial camellia oil production. Through selective adsorption, pre-washing, and ethanol-driven desorption, the applied Pp-A enabled the direct isolation of high-purity TS (~96%) with a recovery ratio > 90%. Notably, Pp-A exhibited excellent operational stability and is of high potential for long-term industrial application. CONCLUSION: Results ensured the practical feasibility of the prepared porous adsorbents in purifying TS, and the proposed methodology is a promising industrial-scale purification strategy. © 2023 Society of Chemical Industry.
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Camellia , Saponinas , Contaminantes Químicos del Agua , Purificación del Agua , Camellia/química , Porosidad , Micelas , Polímeros , Adsorción , Té/química , Etanol , Cinética , Contaminantes Químicos del Agua/química , Purificación del Agua/métodosRESUMEN
An integrated process of electrochemical pre-treatment with carrier-based membrane bioreactor (MBR) was constructed for fresh leachate from waste transfer stations with high organic and NH4+-N content. Results showed that within a hydraulic retention time 40 h, the removal efficiencies of chemical oxygen demand (COD), NH4+-N, suspended solids (SS) and total phosphorus (TP) were over 98.5%, 91.2%, 98.3% and 98.4%, respectively, with the organic removal rate of 18.7 kg/m3. The effluent met the Grade A Standard of China (GB/T31962-2015). Pre-treatment contributed about 70 % of the degraded refractory organics and almost all the SS, with the transformation of the humic-like acid to readily biodegradable organics. Biotreatment further removed over 50% of nitrogen pollutants through simultaneous nitrification and denitrification (SND) and consumed about 30% of organics. Meanwhile, the addition of carriers in the oxic MBR enhanced the attached biomass and denitrification enzyme activity, alleviating membrane fouling.
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Reactores Biológicos , Nitrificación , Nitrógeno/química , Fósforo , Análisis de la Demanda Biológica de OxígenoRESUMEN
BACKGROUND: Heart failure (HF), caused by stress cardiomyopathy, is a major cause of mortality. Cardiac fibrosis is an essential structural remodeling associated with HF; therefore, preventing cardiac fibrosis is crucial to decelerating the progression of HF. Sodium houttuyfonate (SH), an extract of Houttuynia cordata, has a potent therapeutic effect on hypoxic cardiomyocytes in a myocardial infarction model. PURPOSE: To investigate the preventative and therapeutic effects of SH during isoproterenol (ISO)-induced HF and explore the pharmacological mechanism of SH in alleviating HF. METHODS: We analyzed the overlapping target genes between SH and cardiac fibrosis or HF using a network pharmacology analytical method. We verified the suppressive effect of SH on ISO-induced proliferation and activation of cardiac fibroblasts by immunohistochemical staining and histological analysis in an isoproterenol-induced HF mouse model. Additionally, we investigated the effect of SH by evaluating fibrosis and cardiac remodeling markers. To further decipher the pharmacological mechanism of SH against cardiac fibrosis and HF, we performed a molecular docking analysis between SH and hub common target genes. RESULTS: There were 20 overlapping target genes between SH and cardiac fibrosis and 32 overlapping target genes between SH and HF. The 16 common target genes of SH against cardiac fibrosis and HF included MMP2 (matrix metalloproteinase 2), and p38. SH significantly inhibited the ISO- or TGF-ß-induced expression of Col1α (collagen 1), α-SMA (smooth muscle actin), MMP2, TIMP2 (tissue inhibitor of metalloproteinase 2), TGF-ß (transforming growth factor), and Smad2 phosphorylation. Moreover, both ISO- and TGF-ß-induced p38 phosphorylation was inhibited. Molecular docking analysis showed that SH forms a stable complex with MMP2 and p38. CONCLUSIONS: In addition to protecting cardiomyocytes, SH directly inhibits cardiac fibroblast activation and proliferation by binding to MMP2 and p38, subsequently delaying cardiac fibrosis and HF progression. Our prevention- and intervention-based approaches in this study showed that SH inhibited the development of stress cardiomyopathy-mediated cardiac fibrosis and HF when SH was administered before or after the initiation of cardiac stress.
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Cardiomiopatías , Insuficiencia Cardíaca , Cardiomiopatía de Takotsubo , Ratones , Animales , Metaloproteinasa 2 de la Matriz , Isoproterenol , Inhibidor Tisular de Metaloproteinasa-2 , Cardiomiopatía de Takotsubo/patología , Simulación del Acoplamiento Molecular , Insuficiencia Cardíaca/inducido químicamente , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/patología , Miocitos Cardíacos/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Fibrosis , Factor de Crecimiento Transformador beta1/metabolismo , Miocardio/metabolismoRESUMEN
Lake Luoma is an important storage lake for the Eastern route of the South-to-North Water Diversion Project (NSBD), which has many functions including flood control and irrigation, drinking water supply, and ecological maintenance. In order to understand the succession patterns and driving factors of water quality in Lake Luoma, we used monthly monitoring data from 2009 to 2020 in combination with historical data from 1996 to 2008. The long-term succession patterns, seasonal dynamics, and spatial patterns of total nitrogen (TN), total phosphorus (TP), permanganate index, and ammonia nitrogen (NH+4-N) were examined, and the influence of meteorological and hydrological factors on water quality was explored through correlation analyses and generalized additive models. The results showed that it remained in the status of grade â £-inferior â ¤ over the past 25 years. The concentration of TN, which was the main pollutant, changed significantly (1.06-3.49 mg·L-1), experiencing three stages of gradual decline (1996-2002), significant interannual fluctuation (2002-2015), and significant increase (2015-2020). Permanganate index decreased significantly (2.97-6.38 mg·L-1), whereas TP and NH+4-N concentration fluctuated slightly, ranging from 0.024-0.076 mg·L-1 and 0.11-0.69 mg·L-1, respectively. The concentration of TN and TP increased abnormally in the summer of 2017-2020, reaching 3.30 mg·L-1 and 0.14 mg·L-1 in August, respectively, which was approximately 1.5 and 2.4 times the annual average. In terms of seasonal dynamics, the seasonal variation in water quality between summer/autumn and winter/spring reversed after 2015, with water quality in summer/autumn being worse than that in winter and spring, indicating the exacerbation of eutrophication. The water quality in the southern area was obviously better than that in the northern area. The input of pollutants from the Yihe River and Middle Canal increased with water quantity since 2015, which drove the water quality deterioration through nutrients. Our results suggested that the water quality of Lake Luoma should be improved by strengthening exogenous pollution reduction, endogenous control, polder dismantling, and ecological restoration.
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Contaminantes Ambientales , Contaminantes Químicos del Agua , Calidad del Agua , Lagos , Monitoreo del Ambiente/métodos , Inundaciones , Fósforo/análisis , Nitrógeno/análisis , Eutrofización , Contaminantes Químicos del Agua/análisis , Contaminantes Ambientales/análisis , ChinaRESUMEN
Cryopreservation may reduce sperm fertility due to cryodamage including physical-chemical and oxidative stress damages. As a powerful antioxidant, melatonin has been reported to improve cryoprotective effect of sperm. However, the molecular mechanism of melatonin on cryopreserved ram sperm hasn't been fully understand. Give this, this study aimed to investigate the postthaw motility parameters, antioxidative enzyme activities and lipid peroxidation, as well as proteomic, metabolomic changes of Huang-huai ram spermatozoa with freezing medium supplemented with melatonin. Melatonin was firstly replenished to the medium to yield five different final concentrations: 0.1, 0.5, 1.0, 1.5, and 2.0 mM. A control (NC) group without melatonin replenishment was included. Protective effects of melatonin as evidenced by postthaw motility, activities of T-AOC, T-SOD, GSH-Px, CAT, contents of MDA, 4-HNE, as well as acrosome integrity, plasma membrane integrity, with 0.5 mM being the most effective concentration (MC group). Furthermore, 29 differentially abundant proteins involving in sperm functions were screened among Fresh, NC and MC groups of samples (n = 5) based on the 4D-LFQ, with 7 of them upregulated in Fresh and MC groups. 26 differentially abundant metabolites were obtained involving in sperm metabolism among the three groups of samples (n = 8) based on the UHPLC-QE-MS, with 18 of them upregulated in Fresh and MC groups. According to the bioinformatic analysis, melatonin may have positive effects on frozen ram spermatozoa by regulating the abundance changes of vital proteins and metabolites related to sperm function. Particularly, several proteins such as PRCP, NDUFB8, NDUFB9, SDHC, DCTN1, TUBB6, TUBA3E, SSNA1, as well as metabolites like L-histidine, L-targinine, ursolic acid, xanthine may be potential novel biomarkers for evaluating the postthaw quality of ram spermatozoa. In conclusion, a dose-dependent replenishment of melatonin to freezing medium protected ram spermatozoa during cryopreservation, which can improve motility, antioxidant enzyme activities, reduce levels of lipid peroxidation products, modify the proteomic and metabolomic profiling of cryopreserved ram spermatozoa through reduction of oxidative stress, maintenance of OXPHOS and microtubule structure. SIGNIFICANCE: Melatonin, a powerful antioxidant protects ram spermatozoa from cryopreservation injuries in a dose-dependent manner, with 0.5 mM being the most effective concentration. Furthermore, sequencing results based on the 4D-LFQ combined with the UHPLC-QE-MS indicated that melatonin modifies proteomic and metabolomic profiling of ram sperm during cryopreservation. According to the bioinformatic analysis, melatonin may have positive effects on frozen ram spermatozoa by regulating the expression changes of vital proteins and metabolites related to sperm metabolism and function. Particularly, several potential novel biomarkers for evaluating the postthaw quality of ram spermatozoa were acquired, proteins such as PRCP, NDUFB8, NDUFB9, SDHC, DCTN1, TUBB6, TUBA3E, SSNA1, as well as metabolites like L-histidine, L-targinine, ursolic acid, xanthine.
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Melatonina , Preservación de Semen , Animales , Masculino , Antioxidantes/farmacología , Antioxidantes/metabolismo , Criopreservación/métodos , Histidina/metabolismo , Histidina/farmacología , Melatonina/farmacología , Melatonina/metabolismo , Proteómica , Semen , Preservación de Semen/métodos , Ovinos , Motilidad Espermática , Espermatozoides/metabolismo , Xantinas/metabolismo , Xantinas/farmacología , Metabolómica , Ácido UrsólicoRESUMEN
CONTEXT: Stroke is an illness with high morbidity, disability and mortality that presents a major clinical challenge. Sanhua decoction (SHD) has been widely used to treat ischaemic stroke in the clinic. However, the potential mechanism of SHD remains unknown. OBJECTIVE: To elucidate the multitarget mechanism of SHD in ischaemic stroke through network pharmacology and bioinformatics analyses. MATERIALS AND METHODS: Network pharmacology and experimental validation approach was used to investigate the bioactive ingredients, critical targets and potential mechanisms of SHD against ischaemic stroke. Four herbal names of SHD, 'ischemic stroke' or 'stroke' was used as a keyword to search the relevant databases. SH-SY5Y cells were treated with various concentrations of SHD (12.5, 25, 50 or 100 µg/mL) for 4 h, exposed to oxygen and glucose deprivation (OGD) for 1 h, then reoxygenation for 24 h. The cell viability was detected by MTT, the lactate dehydrogenase (LDH) was evaluated by ELISA, and protein expression was detected by western blots. RESULTS: SHD treatment increased the survival rate from 65.9 ± 4.3 to 85.56 ± 5.7%. The median effective dose (ED50) was 47.1 µg/mL, the LDH decreased from 288.0 ± 12.0 to 122.8 ± 9.1 U/L and the cell apoptosis rate decreased from 33.6 ± 1.8 to 16.3 ± 1.2%. Western blot analysis revealed that SHD increased the levels of p-PI3k, p-Akt and p-CREB1, and decreased the expression of TNF-α and IL-6. DISCUSSION AND CONCLUSIONS: This study suggests that SHD protects against cerebral ischaemic injury via regulation of the PI3K/Akt/CREB1 and TNF pathways.
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Isquemia Encefálica/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Relación Dosis-Respuesta a Droga , Medicamentos Herbarios Chinos/administración & dosificación , Humanos , Farmacología en Red , Neuroblastoma/metabolismo , Fosfatidilinositol 3-Quinasa/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Near-infrared (NIR) laser-induced phototherapy through NIR agents has demonstrated the great potential for cancer therapy. However, insufficient tumor killing due to the nonuniform heat or cytotoxic singlet oxygen (1O2) distribution over tumors from phototherapy results in tumor recurrence and inferior outcomes. To achieve high tumor killing efficacy, one of the solutions is to employ the combinational treatment of phototherapy with other modalities, especially with chemotherapeutic agents. In this paper, a simple and effective multimodal therapeutic system was designed via combining chemotherapy, photothermal therapy (PTT), and photodynamic therapy (PDT) to achieve the polytherapy of malignant glioma which is one of the most aggressive tumors in the brain. IR-780 (IR780) dye-labeled tube-forming peptoids (PepIR) were synthesized and self-assembled into crystalline nanotubes (PepIR nanotubes). These PepIR nanotubes showed an excellent efficacy for PDT/PTT because the IR780 photosensitizers were effectively packed and separated from each other within crystalline nanotubes by tuning IR780 density; thus, a self-quenching of these IR780 molecules was significantly reduced. Moreover, the efficient DOX loading achieved due to the nanotube large surface area contributed to an efficient and synergistic chemotherapy against glioma cells. Given the unique properties of peptoids and peptoid nanotubes, we believe that the developed multimodal DOX-loaded PepIR nanotubes in this work offer great promises for future glioma therapy in clinic.
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Perchlorate is a new type of persistent pollutant, which interferes with the synthesis and secretion of thyroxine and affects human health. The EU's limit for perchlorate in tea is 750 µg kg-1. The surface-enhanced Raman scattering (SERS) technique has the characteristics of a simple pretreatment method, rapid detection, high sensitivity, high specificity and great stability in the detection of perchlorate. This study proposed a novel superhydrophobic SERS substrate, which can be used to detect perchlorate in tea. Firstly, a chemical deposition method was used to deposit a silver film on the surface of a thin layer of polydimethylsiloxane. After drying, the substrate was immersed in 1H,1H,2H,2H-perfluorodecyltriethoxysilane aqueous solution for 15 hours to make the surface of the substrate superhydrophobic. Then cysteine molecules were deposited on the surface of the silver film/polydimethylsiloxane by incubation. The superhydrophobic surface has a unique enrichment effect on the highly diluted solution, and perchlorate has a strong affinity for the amino group of cysteine. We collected the Raman spectra of 9 gradient concentrations (1-100 µmol L-1) of perchlorate-spiked tea samples on the hydrophobic substrate, and a linear model of the relationship between the SERS spectral intensity and the concentrations of perchlorate in tea was established. This method reached a good limit of detection of 0.0067 µmol L-1 (0.82 µg kg-1) in tea, which showed that the developed sensor has high sensitivity and could be used as a fast and simple technique for quantitative detection of perchlorate based on SERS technology.
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Cisteína , Plata , Dimetilpolisiloxanos , Humanos , Percloratos , TéRESUMEN
OBJECTIVE: To elucidate the underlying mechanism of Panax notoginseng saponin (PNS) on gastric epithelial cell injury and barrier dysfunction induced by dual antiplatelet (DA). METHODS: Human gastric mucosal epithelial cell (GES-1) was cultured and divided into 4 groups: a control, a DA, a PNS+DA and a LY294002+PNS+DA group. GES-1 apoptosis was detected by flow cytometry, cell permeability were detected using Transwell, level of prostaglandins E2 (PGE2), 6-keto-prostaglandin F1α (6-keto-PGF1α) and vascular endothelial growth factor (VEGF) in supernatant were measured by enzyme linked immunosorbent assay (ELISA), expression of phosphatidylinositide 3-kinase (PI3K), phosphorylated-PI3K (p-PI3K), Akt, phosphorylated-Akt (p-Akt), cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), glycogen synthase kinase-3ß (GSK-3ß) and Ras homolog gene family member A (RhoA) were measured by Western-blot. RESULTS: DA induced apoptosis and hyper-permeability in GES-1, reduced supernatant level of PGE2, 6-keto-PGF1α and VEGF (P<0.05). Addition of PNS reduced the apoptosis of GES-1 caused by DA, restored the concentration of PGE2, 6-keto-PGF1α and VEGF (P<0.05). In addition, PNS attenuated the alteration of COX-1 and COX-2 expression induced by DA, up-regulated p-PI3K/p-Akt, down-regulated RhoA and GSK-3ß. LY294002 mitigated the effects of PNS on cell apoptosis, cell permeability, VEGF concentration, and expression of RhoA and GSK-3ß significantly. CONCLUSIONS: PNS attenuates the suppression on COX/PG pathway from DA, alleviates DA-induced GES-1 apoptosis and barrier dysfunction through PI3K/Akt/ VEGF-GSK-3ß-RhoA network pathway.
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Panax notoginseng , Saponinas , Ciclooxigenasa 1 , Células Epiteliales/metabolismo , Glucógeno Sintasa Quinasa 3 beta , Humanos , Fosfatidilinositol 3-Quinasas/metabolismo , Inhibidores de Agregación Plaquetaria , Proteínas Proto-Oncogénicas c-akt/metabolismo , Saponinas/farmacología , Factor A de Crecimiento Endotelial Vascular , Proteína de Unión al GTP rhoARESUMEN
High platelet reactivity and gastric mucosal injury after aspirin (ASA) treatment are associated with poor compliance and an increased risk of cardiovascular events. Panax notoginseng saponins (PNS) have been widely used for the treatment of coronary heart disease (CHD) in addition to antiplatelet drugs in China; however, the joint effect and possible mechanism of PNS in addition to ASA on platelet activation and gastric injury remain unclear. This study was designed to investigate the combinational effects of PNS with ASA, and to explore the underlying mechanism via arachidonic acid (AA) metabolism pathway using lipidomic analysis. In a randomized, assessor-blinded trial, 42 patients with stable coronary heart disease (SCHD) and chronic gastritis were randomly assigned to receive ASA (nâ¯=â¯21) or PNSâ¯+â¯ASA (nâ¯=â¯21) for 2 months. Compared with ASA alone, PNSâ¯+â¯ASA further inhibited CD62p expression, GPIIb-IIIa activation and platelet aggregation and led to increased platelet inhibition rate. PNSâ¯+â¯ASA suppressed the activity of platelet cyclooxygenase (COX)-1, and decreased the production of TXB2, PGD2, PGE2, 11-HETE, the downstream oxylipids of AA/COX-1 pathway in platelets, compared with ASA alone. The severity of dyspepsia assessment (SODA) results showed that patients in PNSâ¯+â¯ASA group exhibited relieved dyspeptic symptoms as compared with those in ASA group, which might be associated with enhanced secretion of gastrin and motilin. In vivo study of myocardial infarction rats demonstrated that PNS attenuated ASA-induced gastric mucosal injury, which was related to markedly boosted gastric level of 6,15-diketo-13,14-dihydro-prostaglandin (PG)F1α, 13,14-dihydro-15-keto-PGE2 and PGE2 from AA/PG pathway in response to PNSâ¯+â¯ASA compared with ASA alone. In summary, our study demonstrated that the combination of PNS and ASA potentiated the antiplatelet effect of ASA via AA/COX-1/TXB2 pathway in platelets, and mitigated ASA-related gastric injury via AA/PG pathway in gastric mucosa.
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Ácido Araquidónico/metabolismo , Aspirina/uso terapéutico , Plaquetas/efectos de los fármacos , Enfermedad Coronaria/tratamiento farmacológico , Mucosa Gástrica/efectos de los fármacos , Gastritis/tratamiento farmacológico , Fármacos Gastrointestinales/uso terapéutico , Panax notoginseng , Extractos Vegetales/uso terapéutico , Activación Plaquetaria/efectos de los fármacos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Saponinas/uso terapéutico , Adulto , Anciano , Animales , Aspirina/efectos adversos , Beijing , Plaquetas/metabolismo , Enfermedad Crónica , Enfermedad Coronaria/diagnóstico , Enfermedad Coronaria/metabolismo , Citoprotección , Sinergismo Farmacológico , Femenino , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patología , Gastritis/diagnóstico , Gastritis/metabolismo , Fármacos Gastrointestinales/efectos adversos , Fármacos Gastrointestinales/aislamiento & purificación , Humanos , Lipidómica , Masculino , Persona de Mediana Edad , Panax notoginseng/química , Extractos Vegetales/efectos adversos , Extractos Vegetales/aislamiento & purificación , Inhibidores de Agregación Plaquetaria/efectos adversos , Ratas Wistar , Saponinas/efectos adversos , Saponinas/aislamiento & purificación , Factores de Tiempo , Resultado del TratamientoRESUMEN
Anticancer drug-loaded nanoparticles have been explored extensively to decrease side effects while improving their therapeutic efficacy. However, due to the low drug loading content, premature drug release, nonstandardized carrier structure, and difficulty in predicting the fate of the carrier, only a few nanomedicines have been approved for clincial use. Herein, a carrier-free nanoparticle based on the self-assembly of the curcumin-erlotinib conjugate (EPC) is developed. The EPC nanoassembly exhibits more potent cell killing, better antimigration, and anti-invasion effects for BxPC-3 pancreatic cancer cells than the combination of free curcumin and erlotinib. Furthermore, benefiting from both passive and active tumor targeting effect, EPC nanoassembly can effectively accumulate in the tumor tissue in a xenograft pancreatic tumor mouse model. Consequently, EPC effectively reduces the growth of pancreatic tumors and extends the median survival time of the tumor-bearing mice from 22 to 68 days. In addition, no systemic toxicity is detected in the mice receiving EPC treatment. Attributed to the uniformity of the curcumin-erlotinib conjugate and easiness of scaling up, it is expected that the EPC can be translated into a powerful tool in fighting against pancreatic cancer and other epidermal growth factor receptor positive cancers.
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Antineoplásicos , Curcumina , Nanopartículas , Neoplasias Pancreáticas , Animales , Antineoplásicos/uso terapéutico , Línea Celular Tumoral , Curcumina/uso terapéutico , Clorhidrato de Erlotinib , Ratones , Neoplasias Pancreáticas/tratamiento farmacológico , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Photothermal therapy (PTT) has attracted tremendous attention due to its noninvasiveness and localized treatment advantages. However, heat shock proteins (HSPs) associated self-preservation mechanisms bestow cancer cells thermoresistance to protect them from the damage of PTT. To minimize the thermoresistance of cancer cells and improve the efficacy of PTT, an integrated on-demand nanoplatform composed of a photothermal conversion core (gold nanorod, GNR), a cargo of a HSPs inhibitor (triptolide, TPL), a mesoporous silica based nanoreservoir, and a photothermal and redox di-responsive polymer shell is developed. The nanoplatform can be enriched in the tumor site, and internalized into cancer cells, releasing the encapsulated TPL under the trigger of intracellular elevated glutathione and near-infrared laser irradiation. Ultimately, the liberated TPL could diminish thermoresistance of cancer cells by antagonizing the PTT induced heat shock response via multiple mechanisms to maximize the PTT effect for cancer treatment.
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Oro , Terapia Fototérmica , Diterpenos , Compuestos Epoxi , Oxidación-Reducción , Fenantrenos , Fototerapia , TemperaturaRESUMEN
PC (phosphatidylcholine), PE (phosphatidylethanolamine), PI (phosphatidylinositol), and PA (phosphatidic acid) in 9 peanut matrices obtained during the AEP (aqueous extraction processing) of peanut were quantified employing HPLC-ELSD analysis in this study. Phosphorus contents of crude oils obtained from different demulsification treatments were also investigated. Decantation had a larger effect than grinding in terms of phospholipids loss due to alkaline-hydrolysis, indicating this processing step was vital for the manipulation of phospholipids levels remained in oil. Over 80% of initial phospholipids were lost during AEP and only 19.8% of initial phospholipids ended up in cream, skim and sediment phase. 52.55% of the remained phospholipids trapped in cream phase. Just 22.16-32.61 mg/kg phosphorus content could be detected in crude oils, which indicated the separation of phospholipids from the cream phase into aqueous medium. Degumming was not essential in AEP of peanut and the waste generated after demulsification could be a source of phospholipids.
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Arachis/química , Industria de Procesamiento de Alimentos/métodos , Aceite de Cacahuete/análisis , Fosfolípidos/análisis , Fosfolípidos/química , Fósforo/análisis , Cromatografía Líquida de Alta Presión , Emulsiones/química , Aceite de Cacahuete/química , Fosfolípidos/aislamiento & purificación , Extractos Vegetales/química , Reproducibilidad de los Resultados , AguaRESUMEN
Revegetation is considered as an effective approach for desertification control, and artificial sand-binding vegetation exerts a significant contributor to carbon cycling in arid and semiarid regions; however, this is largely determined by the rainfall regime. We measured carbon fluxes (the net ecosystem CO2 exchange (NEE), the gross ecosystem productivity (GEP) and the ecosystem respiration (Reco)) during the growing season of 2014-2016 using the eddy covariance technique and explored the effects of rainfall variables (amount, timing distribution and pulse size) and environmental factors on carbon fluxes at different time scales. The system had NEE values of -117.5 and -98.9 g C m-2 during the growing seasons of 2015 (dry year) and 2016 (wet year), respectively. When the rainfall amount did not differ significantly between spring and autumn, the cumulative GEP was greater in spring than in autumn, whereas the cumulative Reco and NEE showed the opposite pattern. Small (<5 mm) rain events failed to trigger obvious GEP and NEE pulses, whereas ≥ 5 mm or a series of small rain events led to high assimilation but with hysteresis. The magnitude of Reco increased as the rain pulses increased. The Random Forest (RF) algorithm revealed that soil water contents had a great impact on carbon fluxes at different integration periods. A correlation analysis showed that the soil water contents were positively correlated with GEP and Reco and negatively correlated with NEE over different time scales in most cases. These findings suggest that artificial vegetation not only improves habitat restoration but is a significant carbon sink during both dry and wet growing season, which is likely to supplement our knowledge gap to accurately evaluate the current carbon budget in dry land.
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Ecosistema , Arena , Carbono , Ciclo del Carbono , Dióxido de Carbono , Estaciones del AñoRESUMEN
Effect of superfine grinding on pectin extraction was investigated. Sunflower heads were grinded into microparticles of ~50 µm, thus pectin chains were fully exposed due to cell wall breakdown. A good pectin yield of 14.5 ± 0.36% (w/w) was subsequently achieved at mild conditions (pH 5.0, 25 °C, 2 h) associated with 0.8% (w/v) sodium citrate (SC). However, the molecule weight of pectin was greatly reduced (Mw = 7.87 ± 0.21 kDa) due to the action of endo-pectinases. With heating (pH 5.0, 85 °C for 20 min, 25 °C for 1.5 h) the endo-pectinases were effectively inhibited, thus Mw was increased to 338.07 ± 12.37 kDa. With superfine grinding, pectin extracted with different conditions presented various properties. Pectin extracted at pH 2.5 had higher esterification degree (DE, ~40%) and gelled at 3% (w/v) concentration. In contrast, pectin extracted under mild condition with low DE (21%) cannot gel at the same concentration. Conclusively, superfine grinding has potential application in pectin extraction.
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Helianthus/química , Pectinas/química , Esterificación , Calor , Peso Molecular , Pectinas/aislamiento & purificaciónRESUMEN
The interfacial properties of ultrahigh methoxylated pectin (UHMP) prepared via esterification of citrus pectin (CP) were investigated. The intrinsic viscosity ([η]) of pectin was significantly decreased from 1211.5 mL/g to 294.9 mL/g as the degree of methylation (DM) increased from 63.18 ± 0.08% to 91.52 ± 0.11%. Surface tension (γ) analysis indicated that UHMP had a critical micelle concentration (CMC) of 0.8 g/L, which was slightly smaller than that of sugar beet pectin (SBP) (1.0 g/L). The morphology of the UHMP aggregation presented a network structure and irregular clusters at 10 µg/mL and 1 µg/mL based on atomic force microscopy (AFM). Transmission electron microscopy (TEM) observations further confirmed the self-aggregation behaviours and rod-like micelles of UHMP. The surface excess (Γ) was 1.69 ± 0.17 µmol/m2 for UHMP, which was lower than the values of SBP (1.88 ± 0.21 µmol/m2) and CP (2.91 ± 0.57 µmol/m2). Correspondingly, UHMP possessed the highest molecular area (A) of 0.99 ± 0.10 nm2. Thus, UHMP was proposed to be more flexible and extendable at the interface. The interfacial shear rheology study suggested that UHMP was able to form an elastic-dominant interfacial film to stabilize the oil/water interface.
Asunto(s)
Beta vulgaris/metabolismo , Micelas , Pectinas/química , Emulsiones , Cinética , Microscopía de Fuerza Atómica , Microscopía Electrónica de Transmisión , Peso Molecular , Tamaño de la Partícula , Reología , Resistencia al Corte , Propiedades de Superficie , Tensión Superficial , ViscosidadRESUMEN
BACKGROUND: There is a controversy in terms of the efficacy of vitamin D supplementation in improving asthma symptom control. Moreover, whether there is a difference in the treatment effect with respect to baseline vitamin D status remains unknown. This meta-analysis was to assess the correlations of vitamin D status with asthma-related respiratory outcomes. METHODS: PubMed, EMBASE, and Cochrane Library were searched for randomized controlled trials of vitamin D supplementation in patients with asthma. Primary outcomes were the rate of asthma exacerbation and predicted percentage of forced expiratory volume in first second (FEV1%). Secondary outcomes were asthma control test (ACT) scores, fractional exhaled nitric oxide (FeNO), interleukin-10 (IL-10) and adverse events. RESULTS: A total of 14 randomized controlled trials (1421 participants) fulfilled the inclusion. Vitamin D supplementation was associated with a significant reduction in the rate of asthma exacerbation by 27% (RR: 0.73 95%Cl (0.58-0.92)). In subgroup analysis, the protective effect of exacerbation was restricted in patients with vitamin D insufficiency (vitamin Dâ¯<â¯30â¯ng/ml) (RR: 0.76 95%Cl (0.61-0.95)). An improvement of FEV1% was demonstrated in patients with vitamin D insufficiency and air limitation (FEV1%â¯<â¯80%) (MD: 8.3 95%Cl (5.95-10.64). No significant difference was observed in ACT scores, FeNO, IL-10 and adverse events. CONCLUSIONS: Vitamin D supplementation reduced the rate of asthma exacerbation, especially in patients with vitamin D insufficiency. Additionally, the benefit of vitamin D had a positive effect on pulmonary function in patients with air limitation and vitamin D insufficiency.
Asunto(s)
Asma/tratamiento farmacológico , Evaluación de Síntomas/métodos , Vitamina D/uso terapéutico , Vitaminas/uso terapéutico , Adolescente , Adulto , Anciano , Asma/metabolismo , Asma/fisiopatología , Niño , Preescolar , Progresión de la Enfermedad , Espiración , Femenino , Volumen Espiratorio Forzado/efectos de los fármacos , Humanos , Lactante , Interleucina-10/análisis , Masculino , Persona de Mediana Edad , Óxido Nítrico/análisis , Ensayos Clínicos Controlados Aleatorios como Asunto , Pruebas de Función Respiratoria/métodos , Evaluación de Síntomas/estadística & datos numéricos , Resultado del Tratamiento , Vitamina D/efectos adversos , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/tratamiento farmacológico , Deficiencia de Vitamina D/epidemiología , Vitaminas/efectos adversosRESUMEN
Ultrahigh methoxylated pectin (UHMP) was prepared by esterification of citrus pectin in absolute methanol at 60⯰C for 12â¯h, whereby its methoxylation degree was increased from 63.18⯱â¯0.08% to 91.20⯱â¯0.13%, and its molecular weight was reduced from 64,400â¯g/mol to 15,000â¯g/mol. Structural modifications improved UHMP solubility by over 5%(w/v) and resulted in a flat reduced viscosity profile that was slightly affected by pectin concentration increase and pH change. Interfacial activity of UHMP was improved since most of the galacturonic acid (GalA) units had one methyl group and two hydroxyl groups. Dynamic interfacial tension analysis indicated that UHMP was adsorbed at O/W interface faster than mother pectin with a better capacity to reduce the initial interfacial tension. UHMP emulsions prepared by phase inversion method at different solid-to-oil ratios (20-50%) had a small Z-average size of approximately 400â¯nm with a creaming index (CI) of 17-20%. During long-term storage (56â¯days), droplet size and CI were monitored every 7â¯days, and results suggested that UHMP emulsions were stable. UHMP emulsions showed good pH stability after 14-days storage in a wide pH range of 2-8 without droplet coalescence. Thermal treatment at 85⯰C accelerated the flotation of large droplets but did not break droplets.