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Dredged soil and phosphogypsum (PG) are waste materials that must be treated to reduce their negative environmental effects. Guided by the concept of waste treatment, this study proposed the use of PG as a supplementary cementitious material to stabilize waste-dredged soil, and calcium aluminate cement (CAC) was selected to further improve the strength of the cement-treated dredged soil. Several laboratory tests were conducted to investigate the pH, unconfined compressive strength (UCS), and failure strain of the cement-treated soils in different proportions. Microstructural and mineralogical tests were performed to reveal the mechanisms underlying the strength improvement of PG and CAC. The results showed that both PG and CAC enhanced the strength of cement-treated dredged soil. PG provided SO2- 4 to promote the formation of ettringite (aluminum ferrite trisulfate (AFt)), whereas CAC neutralized the acidity of PG and provided reactants to the reaction system, leading to an increase in the pH and strength with an increase in the relative CAC content. Meanwhile, an exponential relationship was obtained between pH and qu. Mineralogical changes demonstrated that the major hydration products of cementitious materials, such as calcium silicate (aluminate) hydrate (C-(A)-S-H), AFt, and calcium aluminate hydrate (C-A-H), enhanced the strength by filling pores between particles and bridging soil particles. However, excess CAC content may not be favorable for the later strength formation, the relative CAC content is recommended to be in the range of 40%-60%. Compared to using sand, the construction of a square kilometer of reclamation consumed 3.5 million tons of PG, and saved 1.54 billion USD by using dredged soil as raw material. Hence, the use of PG to treat dredged soils will have great environmental sustainability, economic benefits, and engineering value.
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Compuestos de Aluminio , Compuestos de Calcio , Fósforo , Suelo , Residuos Sólidos , Sulfato de CalcioRESUMEN
Understanding strongly correlated quantum materials, such as high-T_{c} superconductors, iron-based superconductors, and twisted bilayer graphene systems, remains as one of the outstanding challenges in condensed matter physics. Quantum simulation with ultracold atoms in particular optical lattices, which provide orbital degrees of freedom, is a powerful tool to contribute new insights to this endeavor. Here, we report the experimental realization of an unconventional Bose-Einstein condensate of ^{87}Rb atoms populating degenerate p orbitals in a triangular optical lattice, exhibiting remarkably long coherence times. Using time-of-flight spectroscopy, we observe that this state spontaneously breaks the rotational symmetry and its momentum spectrum agrees with the theoretically predicted coexistence of exotic stripe and loop-current orders. Like certain strongly correlated electronic systems with intertwined orders, such as high-T_{c} cuprate superconductors, twisted bilayer graphene, and the recently discovered chiral density-wave state in kagome superconductors AV_{3}Sb_{5} (A=K, Rb, Cs), the newly demonstrated quantum state, in spite of its markedly different energy scale and the bosonic quantum statistics, exhibits multiple symmetry breakings at ultralow temperatures. These findings hold the potential to enhance our comprehension of the fundamental physics governing these intricate quantum materials.
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Aim: To explore the effects of brain-computer interface training combined with mindfulness therapy on Hemiplegic Patients with Stroke. Background: The prevention and treatment of stroke still faces great challenges. Maximizing the improvement of patients' ability to perform activities of daily living, limb motor function, and reducing anxiety, depression, and other social and psychological problems to improve patients' overall quality of life is the focus and difficulty of clinical rehabilitation work. Methods: Patients were recruited from December 2021 to November 2022, and assigned to either the intervention or control group following a simple randomization procedure (computer-generated random numbers). Both groups received conventional rehabilitation treatment, while patients in the intervention group additionally received brain-computer interface training and mindfulness therapy. The continuous treatment duration was 5 days per week for 8 weeks. Limb motor function, activities of daily living, mindfulness attention awareness level, sleep quality, and quality of life of the patients were measured (in T0, T1, and T2). Generalized estimated equation (GEE) were used to evaluate the effects. The trial was registered with the Chinese Clinical Trial Registry (ChiCTR2300070382). Results: A total of 128 participants were randomized and 64 each were assigned to the intervention and control groups (of these, eight patients were lost to follow-up). At 6 months, compared with the control group, intervention group showed statistically significant improvements in limb motor function, mindful attention awareness, activities of daily living, sleep quality, and quality of life. Conclusion: Brain-computer interface combined with mindfulness therapy training can improve limb motor function, activities of daily living, mindful attention awareness, sleep quality, and quality of life in hemiplegic patients with stroke. Impact: This study provides valuable insights into post-stroke care. It may help improve the effect of rehabilitation nursing to improve the comprehensive ability and quality of life of patients after stroke. Clinical review registration: https://www.chictr.org.cn/, identifier ChiCTR2300070382.
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Methylmercury (MeHg) is a toxin that causes severe neuronal oxidative damage. As vitamin C is an antioxidant well-known to protect neurons from oxidative damage, our goal was to elucidate its protective mechanism against MeHg-induced oxidative stress in human neuroblastomas (SHSY5Y). We treated cells with MeHg, L-ascorbic acid 2-phosphate (AA2P), or both, and used MTT, flow cytometry, and Western blot analyses to assess cell damage. We found that MeHg significantly decreased the survival rate of SH-SY5Y cells in a time- and dose-dependent manner, increased apoptosis, downregulated PAR and PARP1 expression, and upregulated AIF, Cyto C, and cleaved Caspase-3 expression. A time course study showed that MeHg increased reactive oxygen species (ROS) accumulation; enhanced apoptosis; increased DNA damage; upregulated expression ofγH2A.X, KU70, 67 and 57 kDa AIF, CytoC, and cleaved Caspase-3; and downregulated expression of 116 kDa PARP1, PAR, BRAC1, and Rad51. Supplementation with AA2P significantly increased cell viability and decreased intrinsic ROS accumulation. It also reduced ROS accumulation in cells treated with MeHg and decreased MeHg-induced apoptosis. Furthermore, AA2P conversely regulated gene expression compared to MeHg. Collectively, we demonstrate that AA2P attenuates MeHg-induced apoptosis by alleviating ROS-mediated DNA damage and is a potential treatment for MeHg neurotoxicity.
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The objective of this study was to investigate the effects of tributyrin supplementation on liver fat metabolism in broiler chickens. Two hundred and forty broilers were randomly allocated into two experimental groups (6 replicates per treatment; 20 chickens in each replicate): the control group (CN), which received a basal diet, and the tributyrin group (TB), which received a basal diet supplemented with 1 g/kg of tributyrin. The experimental period lasted 37 days. The results showed that in the liver, broilers supplemented with tributyrin had higher content of high-density lipoprotein cholesterol (HDL-C) (p < 0.05). Liver hepatic lipase (HL), lipoprotein lipase (LPL) and total lipid (TL) activity were significantly lower than in the TB group than that in the NC group. Meanwhile, the diet supplemented with tributyrin had more lipid droplets than the NC group, whereas the TB and NC groups showed no histological abnormalities in the liver. Furthermore, the mRNA expression levels of peroxisome proliferators-activated receptor α (PPARα), proliferators-activated receptor γ (PPARγ), fatty acid synthase (FAS), LPL and adipose triglyceride lipase (ATGL) in the liver were significantly upregulated in the TB group (p < 0.05), while those of the long-chain acyl-CoA-synthetase 1 (ACSL1) mRNA between the TB group and the NC group were not different (p > 0.05). These findings indicated that the diet supplemented with tributyrin could increase fat deposition appropriately by promoting fat synthesis without causing liver tissue damage, which demonstrated that tributyrin can be considered a valid feed additive for broiler chickens.
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Pollos , Metabolismo de los Lípidos , Animales , Pollos/genética , Pollos/metabolismo , Triglicéridos/farmacología , Triglicéridos/metabolismo , Suplementos Dietéticos , Hígado/metabolismo , ARN Mensajero/metabolismo , Expresión GénicaRESUMEN
To evaluate the safety and efficiency of sunitinib and sorafenib in the treatment of renal cell carcinoma (RCC).Databases were searched up till February 28, 2018. Two reviewers independently assessed trials for eligibility, quality, and extracted relevant data. Results are expressed as risk ratio (RR) or hazard ratio (HR) with 95% confidence intervals (CI). Six studies including 3112 patients were accessed. Sorafenib group exhibited higher median progression-free survival (mPFS) compared to sunitinib group (MD, -1.30; 95% CI, -2.56 to -0.03), especially in the first-line treatment (MD, -1.33; 95% CI, -2.61 to -0.04). However, sunitinib significantly reduced the risk of progression-free survival (PFS) compared to sorafenib (HR, 0.71; 95% CI, 0.6-0.82). Sunitinib also significantly reduced risk of overall survival (OS) compared to sorafenib (HR, 0.79; 95% CI, 0.65-0.92), while median OS was similar in both groups (MD, -0.48; 95% CI, -3.40-2.43). With regards to safety, the risk of rash (RR, 0.31, 95% CI, 0.12-0.79) was greater in sunitinib than sorafenib group, while the risk of decreased appetite (RR 2.10, 95% CI: 1.33-3.30) and dehydration (RR 2.73, 95% CI: 1.14-6.56) was smaller in contrast.Based on risk of PFS and OS, sunitinib was a better treatment option for RCC treatment while patients faced with severe skin reaction. And for those Asian patients classified under MSKCC moderate risk, whether in first or second-line treatment, had difficulty in feeding, sorafenib is a better choice for prolong mPFS.
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Antineoplásicos/uso terapéutico , Carcinoma de Células Renales/tratamiento farmacológico , Neoplasias Renales/tratamiento farmacológico , Sorafenib/uso terapéutico , Sunitinib/uso terapéutico , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Carcinoma de Células Renales/mortalidad , Carcinoma de Células Renales/patología , Supervivencia sin Enfermedad , Humanos , Neoplasias Renales/mortalidad , Neoplasias Renales/patología , Modelos de Riesgos Proporcionales , Sorafenib/administración & dosificación , Sorafenib/efectos adversos , Sunitinib/administración & dosificación , Sunitinib/efectos adversosRESUMEN
Saikosaponin A (SSa) is isolated from the dried root of Radix Bupleuri, an herb widely used in traditional Chinese medicine, exerting antitumor activities. The T helper cell type 1(Th1)/Th2 balance is associated with antitumor immunity in breast cancer. The present study aimed to investigate the effects of SSa on Th1/Th2 balance in breast cancer and to explore the underlying mechanisms. Breast cancer in rats was induced by intragastrical administration of 7,12-dimethyl-benz[a] anthracene once (100 mg/kg). At d91, the rats suffering from tumors were randomly divided into three groups and treated with vehicle solution (control group), tamoxifen (TAM group), and SSa (SSa group) daily for 56 days, respectively. The tumor volume reduction ratio and tumor cell proliferation were detected to assess the antitumor effect of SSa. The positive staining numbers of CD8+ and CD4+ T cells infiltrated in breast tumors were measured by immunohistochemistry to evaluate the antitumor immunity of SSa. Cytokine levels in serum secreted by Th1 cells [interferon gamma (IFN-γ), interleukin (IL)-12] and Th2 cells (IL-4, IL-10) were detected to evaluate Th1/Th2 balance. The related molecules of IL-12/signal transducers and activators of transcription 4 (STAT4) pathway were detected by immunohistochemistry staining, RT-PCR, and Western blot to explore the mechanisms of SSa. The results showed that, compared with the control group, SSa significantly inhibited tumor growth and tumor cell proliferation. SSa enhanced antitumor immunity, which was demonstrated as increased CD8+ T cells and CD4+ T cells infiltrated in tumors. SSa shifted Th1/Th2 balance toward Th1, which was confirmed as increased serum IFN-γ and IL-12 levels, while decreased serum IL-4 and IL-10 levels. SSa increased IL-12, IL-12 receptor, and phosphorylated STAT4 expressions to promote Th1 differentiation. In conclusion, the present work suggested that SSa could inhibit breast cancer growth by shifting Th1/Th2 balance toward Th1. The underlying mechanism may involve activation of the IL-12/STAT4 pathway that induced Th1 differentiation.
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ETHNOPHARMACOLOGICAL RELEVANCE: Vascular dementia (VaD) is the common cognitive disorder derived mainly from lacunar stroke (LS). The oxidative stress induced neurovascular coupling (NVC) dysfunction involves in the pathogenesis of VaD. Currently, there is no specific drug for VaD. Ling-Yang-Gou-Teng -Decoction (LG), a well-known traditional Chinese formula, has been used for preventing VaD in clinic. AIM OF THE STUDY: In this study, we aimed to investigate the underlying mechanism of LG on VaD in rats. MATERIALS AND METHOD: VaD was replicated with autologous micro-thrombi against the background of hypercholesterolemia induced with high fatty diet. PTX (68.90â¯mg/kg/day), LG with three dosages (2.58, 8.14, 25.80â¯g/kg/day) was orally administrated to VaD rats, respectively. The NVC sensitivity was defined as the ratio of the microcirculative cerebral blood velocity (CBV) to the electroencephalograph (EEG) before and after penicillin stimulation. Behavioral performance, pathological changes of brain and oxidation related molecules were detected to assess the effects of LG on VaD. RESULTS: LG exhibited beneficial effects on the VaD, which was demonstrated as improved exploratory, learning and memory abilities, relieved vascular or neural pathological changes in cerebral cortex or hippocampus. LG maintained NVC sensitivity, which was confirmed as significantly increased ΔCBV and the elevated ratio of ΔCBV/ΔqEEG. The underlying mechanisms of LG was associated with antioxidant effects, which was confirmed as significantly decreased nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) expression, and increased superoxide dismutase 3 (SOD3) expression. LG also reduced iNOS, increased nNOS and eNOS expression to restore NO bioavailability. CONCLUSIONS: The results suggested that LG prevented VaD may associate with inhibiting oxidative stress, protecting NO bioavailability, and then maintaining NVC sensitivity.
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Antioxidantes/uso terapéutico , Demencia Vascular/tratamiento farmacológico , Fármacos Neuroprotectores/uso terapéutico , Exudados de Plantas/uso terapéutico , Animales , Antioxidantes/farmacología , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/patología , Demencia Vascular/genética , Demencia Vascular/metabolismo , Demencia Vascular/patología , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , NADPH Oxidasa 2/genética , NADPH Oxidasa 2/metabolismo , Fármacos Neuroprotectores/farmacología , Acoplamiento Neurovascular/efectos de los fármacos , Óxido Nítrico Sintasa de Tipo I/genética , Óxido Nítrico Sintasa de Tipo I/metabolismo , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/metabolismo , Óxido Nítrico Sintasa de Tipo III/genética , Óxido Nítrico Sintasa de Tipo III/metabolismo , Estrés Oxidativo/efectos de los fármacos , Exudados de Plantas/farmacología , Ratas Wistar , Superóxido Dismutasa/genética , Superóxido Dismutasa/metabolismoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Qingdu granule (QDG), a traditional Chinese herbal prescription, had anti-tumor effect on breast cancer. However the underlying mechanism of QDG was unclear. THE AIM OF THIS STUDY: The present study aimed to investigate whether QDG could inhibit angiogenesis of breast cancer via acting on nuclear factor of activated T-cells (NFAT) signaling pathway. This was implicated in human umbilical vein endothelial cells (HUVECs) in vitro and breast cancer xenograft model in vivo. MATERIALS AND METHODS: The VEGF165 (15.58â¯ng/mL) induced human umbilical vein endothelial cells (HUVECs) were treated with serum samples containing tamoxifen (TAM), tacrolimus (FK506), or QDG with three dosages. The migration and canalization capacities of HUVECs were evaluated by transwell migration and tube formation assay. In 72â¯h-cultured HUVECs, The gene expression, protein amount, and nuclear translocation of NFATc3 were measured. The anti-tumor and anti-angiogenic effects of QDG in vivo were investigated in breast cancer xenograft model. The serum VEGF levels, microvessel density, and protein expressions (immunohistochemistry and western blot) of VEGF, VEGFR2 and NFATc3 were detected. RESULTS: The results showed that, QDG significantly inhibited HUVEC migration and tube formation. It downregulated NFATc3 gene expression, decreased NFATc3 protein amount, and reduced the ratio of NFATc3 nuclear translocation in HUVECs. In breast cancer xenograft model, QDG treatment significantly suppressed tumor growth, inhibited VEGF release, and decreased microvessel density. QDG reduced protein expressions of VEGF, VEGFR2 and NFATc3. CONCLUSION: The results suggested that QDG showed anti-angiogenic effects of breast cancer both in vitro and in vivo. The mechanism might be partially associated with inhibiting NFAT signaling pathway.
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Inhibidores de la Angiogénesis/uso terapéutico , Medicamentos Herbarios Chinos/uso terapéutico , Neoplasias Mamarias Experimentales/tratamiento farmacológico , Inhibidores de la Angiogénesis/farmacología , Animales , Movimiento Celular/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Femenino , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/fisiología , Humanos , Células MCF-7 , Neoplasias Mamarias Experimentales/metabolismo , Neoplasias Mamarias Experimentales/patología , Ratones Endogámicos BALB C , Factores de Transcripción NFATC/antagonistas & inhibidores , Factores de Transcripción NFATC/metabolismo , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Carga Tumoral/efectos de los fármacos , Factor A de Crecimiento Endotelial Vascular/sangre , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
OBJECTIVE: To evaluate vitality principle in breast cancer rats by pharmacologically developing a model for anticancer surveillance. METHODS: The breast cancer in rats was replicated with 7,12-Dimethylbenz[a]anthracene (DMBA, i.g., 100 mg/kg) at d001. The anticancer surveillance was defined as the intervals between the primary sensitization and the first challenge stirred with complete Freund's adjuvant (CFA), the various intervals (k = 0.80) were dominated from d025 (600.00 h) to d095 (2288.82 h). The optimal surveillant status was confirmed with the median effective interval (EI50) from tumor volume regressive curve, for developing the pharmacodynamic model. The tumor and tumor infiltrating lymphocyte histopathology was used to confirm the immune surveillance being affected with CFA in breast cancer tumorigenesis. The availability of this model was confirmed with Shugan Liangxue prescription (SLP), from the vitality principle, and assured further from interleukin-12 levels. RESULTS: The regressive curve was set up between the intervals and tumor volumes, the EI50 in SLP-treated rats (1475.00 h, YSLP = 0.1026 + 0.8780/[1 + 10(27.1425-8.565x)]) was postponed, which was 1.87 multiple of the EI50 in CFA rats (791.40 h, y = -0.0525 + 0.9452/[1 + 10(30.4870-10.52x)], so did prepone the curve between the intervals and the immunological biomarker, serum interleukin-12 levels, the EI50 in SLP-treated rats (744.90 h, YSLP = -0.0145 + 0.7455/[1 + 10(52.09636-18.13x)]) be 0.78 multiple of the EI50 in CFA rats (960.10 h, YCFA = 0.2460 + 0.7270/[1 + 10 (-67.1546 + 22.52x)]), this immunological action being mediated the anticancer prognosis. Tumor histology was confirmed the more tumor infiltrating lymphocytes activated in SLP rats with CFA stirred immunity than rats only received CFA. CONCLUSION: The model for anticancer surveillance was pharmacologically established as the optimal interval (791.40 h) between the primary sensitization and the first challenge stirred with complete Freund's adjuvant. This available model was confirmed with SLP, from the vitality principle, for evaluating immunological effects against breast cancer.
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Neoplasias de la Mama/tratamiento farmacológico , Medicamentos Herbarios Chinos/administración & dosificación , Animales , Neoplasias de la Mama/inmunología , Neoplasias de la Mama/fisiopatología , Evaluación Preclínica de Medicamentos , Femenino , Humanos , Interleucina-12/inmunología , Ratas , Ratas Sprague-Dawley , Carga Tumoral/efectos de los fármacosRESUMEN
Oligomeric Aß42 aggregates have been identified as one of the major neurotoxic components of Alzheimer's disease (AD). Immunotherapy targeted against these Aß42 aggregates has been proposed as an appropriate therapeutic approach for the treatment of AD. Here, we report an anti-oligomeric Aß42 single-chain variable fragment (scFv) antibody, named MO6, obtained from the human antibody library of a healthy donor. ScFv MO6 specifically recognized and bound to the oligomeric Aß42 (Aß42 oligomers and immature protofibrils; 18-37 kDa), and reduced their levels mainly by blocking their formation, although scFv MO6 also induced disaggregation of Aß42 aggregates. More importantly, scFv MO6 ameliorated or attenuated Aß42-induced cytotoxicity and increased cell viability by up to 33%. Furthermore, scFv MO6 efficiently passed through an in vitro blood-brain barrier (BBB) model with a delivery efficiency of 66% after 60 min post-administration. ScFv MO6 is a monovalent antibody with an affinity constant (KD) of 5.2×10(-6) M for Aß42 oligomers. Molecular docking simulations of Aß42 to scFv MO6 revealed that the approach and specific binding of scFv MO6 to oligomeric Aß42 aggregates was achieved by conformational recognition and directed induction, which resulted in a more dynamic adaptation of Aß42 to scFv MO6, occurring mainly in the N-terminal (3-4), middle (12-19) and C-terminal (34-42) regions of Aß42. This binding mode of scFv MO6 to Aß42 explains its protective effects against oligomeric Aß42. Our findings may be applied for the design of a smaller antibody specific for Aß42 oligermers.
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Péptidos beta-Amiloides/inmunología , Fármacos Neuroprotectores/farmacología , Fragmentos de Péptidos/inmunología , Anticuerpos de Cadena Única/farmacología , Secuencia de Aminoácidos , Péptidos beta-Amiloides/genética , Animales , Barrera Hematoencefálica/efectos de los fármacos , Barrera Hematoencefálica/metabolismo , Permeabilidad Capilar/efectos de los fármacos , Permeabilidad Capilar/fisiología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Técnicas de Cocultivo , Evaluación Preclínica de Medicamentos , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Simulación del Acoplamiento Molecular , Datos de Secuencia Molecular , Fármacos Neuroprotectores/farmacocinética , Fragmentos de Péptidos/genética , Unión Proteica/efectos de los fármacos , Ratas , Alineación de Secuencia , Anticuerpos de Cadena Única/genética , Anticuerpos de Cadena Única/farmacocinéticaRESUMEN
The aim of the study was to evaluate the pro-apoptotic effects of polysaccharides derived from Lentinus edodes and further elucidated the mechanisms of this action. Our results demonstrated that marked morphological changes of apoptosis were observed after treatment of L. edodes polysaccharides [Lentinan (LTN)]. Moreover, LTN-induced cell apoptosis was characterized by a rapid stimulation of reactive oxygen species production, the loss of mitochondrial membrane potential and an increase in intracellular concentration of Ca(2+) . In addition, the results of the haematoxylin and eosin and TUNEL assay further confirmed that LTN-induced apoptosis in vivo. Furthermore, flow cytometry analysis showed that LTN could arrest the cell cycle at G2/M phase, and immunofluorescence showed LTN caused disruption of microtubule. These results suggest that disruption of cellular microtubule network, arrest of the cell cycle at G2/M phase and induction of apoptosis may be one of the possible mechanisms of anti-tumour effect of LTN.
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Apoptosis/efectos de los fármacos , Puntos de Control de la Fase G2 del Ciclo Celular/efectos de los fármacos , Lentinano/farmacología , Microtúbulos/ultraestructura , Hongos Shiitake/química , Animales , Calcio/metabolismo , División Celular , Línea Celular Tumoral , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Ratones , Especies Reactivas de Oxígeno/metabolismoRESUMEN
A novel polysaccharide named Angelica sinensis polysaccharide (ASP) was obtained from the powdered and defatted roots of A. sinensis (Oliv.) Diels. The molecular weight of ASP was determined to be 78 kDa and was 95.0% sugars consisting of mostly arabinose, glucose, and galactose with a molar ratio of 1:5.68:3.91. A previous study indicated that ASP may increase plasma iron levels by suppressing the expression of hepcidin, a negative regulator of body iron metabolism, in the liver. The present study aims to clarify the inhibitory effect of ASP on hepcidin expression in rat models of iron deficiency anemia (IDA), and clarify the mechanisms involved. It was demonstrated that ASP significantly reduced hepcidin expression by inhibiting the expression of mothers against decapentaplegic protein 4 (SMAD4) in liver and stimulating the secretion of erythropoietin, which further downregulated hepcidin by repressing CCAAT/enhancer-binding protein α (C/EBPα) and the phosphorylation of signal transducer and activator of transcription 3/5. The results indicate that ASP can suppress the expression of hepcidin in rats with IDA, and may be useful for the treatment of IDA.
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Anemia Ferropénica/tratamiento farmacológico , Angelica sinensis/química , Péptidos Catiónicos Antimicrobianos/antagonistas & inhibidores , Péptidos Catiónicos Antimicrobianos/genética , Polisacáridos/farmacología , Anemia Ferropénica/fisiopatología , Animales , Péptidos Catiónicos Antimicrobianos/metabolismo , Arabinosa/aislamiento & purificación , Arabinosa/metabolismo , Proteína alfa Potenciadora de Unión a CCAAT/genética , Proteína alfa Potenciadora de Unión a CCAAT/metabolismo , Regulación hacia Abajo , Eritropoyetina/metabolismo , Hepcidinas , Hierro/sangre , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Fosforilación , Raíces de Plantas/química , Polisacáridos/administración & dosificación , Polisacáridos/aislamiento & purificación , Polvos/administración & dosificación , Polvos/química , Ratas , Ratas Sprague-Dawley , Factor de Transcripción STAT3/genética , Factor de Transcripción STAT3/metabolismo , Factor de Transcripción STAT5/genética , Factor de Transcripción STAT5/metabolismo , Transducción de Señal , Proteína Smad4/genética , Proteína Smad4/metabolismoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Angelica sinensis polysaccharide is an important bioactive component of Angelica sinensis (Oliv.) Diels that has been used in traditional Chinese medicine for treating gynecological disorders and anemia. AIM OF THE STUDY: Previous study indicated that Angelica sinensis polysaccharide (ASP) may promote plasma iron levels by suppressing the expression of hepcidin, a negative regulator of body iron metabolism, in the liver. The present study aims to clarify the inhibitory effect of ASP on hepcidin expression as well as the involved mechanisms. MATERIALS AND METHODS: ASP (1g/kg) or vehicle (normal saline) was intragastrically administrated to rats everyday for 14 d. Intraperitoneal injections of recombinant human erythropoietin (rhEPO, 2000 U/kg) were given to positive control group. Erythropoietin and hepcidin levels in serum at different time points were determined by enzyme-linked immunosorbent assay. Western blot was used to investigate the expression of 6 pertinent signal proteins in liver. RESULTS: ASP significantly reduced hepcidin expression by inhibiting the expression of signal transducer and activator of transcription 3/5 (STAT3/5) and mothers against decapentaplegic protein 4 (SMAD4) in liver and stimulating the secretion of erythropoietin, which further down-regulated hepcidin by repressing CCAAT/enhancer-binding protein α (C/EBPα), SMAD4, and the phosphorylation process of STAT3/5. CONCLUSIONS: ASP can suppress the expression of hepcidin in normal rats, and may be used in the treatments of hepcidin-induced diseases.