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Bushen Tiaoxue Granules (BTG) is an empirical Chinese herbal formula that has been used for the treatment of subfertility. The protective effect of BTG on controlled ovarian hyperstimulation (COH)-induced impaired endometrial receptivity has been reported in our previous study. This study aims to explore the mechanisms of BTG on ameliorating abnormal morphology of endometrium based on network pharmacology. Active compounds of BTG were identified via the traditional Chinese medicine systems pharmacology and UPLC-MS technology. The SwissTargetPrediction platform and HERB database were used to screen out the putative targets of BTG. Potential targets of endometrial dysfunction caused by COH were obtained from three GEO databases. Through the STRING database, the protein-protein interaction was carried out according to the cross-common targets of diseases and drugs. GO terms and KEGG pathways enrichment analyses were conducted via the Metascape database. AutoDock Vina was used for docking validation of the affinity between active compounds and potential targets. Finally, in vivo experiments were used to verify the potential mechanisms derived from network pharmacology study. A total of 141 effective ingredients were obtained from TCMSP and nine of which were verified in UPLC-MS. Six genes were selected through the intersection of 534 disease related genes and 165 drug potential targets. Enrichment analyses showed that BTG might reverse endometrial dysfunction by regulating adherens junction and arachidonic acid metabolism. Hematoxylin-eosin staining revealed that BTG ameliorated the loose and edematous status of endometrial epithelium caused by COH. The protein expression of FOXO1A, ß-Catenin and COX-2 was decreased in the COH group, and was up-regulated by BTG. BTG significantly alleviates the edema of endometrial epithelium caused by COH. The mechanisms may be related to adheren junctions and activation of arachidonic acid metabolism. The potential active compounds quercetin, taxifolin, kaempferol, eriodictyol, and isorhamnetin identified from the BTG exhibit marginal cytotoxicity. Both high and low concentrations of kaempferol, eriodictyol, and taxifolin are capable of effectively ameliorating impaired hESC cellular activity.
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Quempferoles , Farmacología en Red , Femenino , Humanos , Ácido Araquidónico , Cromatografía Liquida , Espectrometría de Masas en Tándem , Endometrio , Simulación del Acoplamiento MolecularRESUMEN
BACKGROUND: Neuroinflammation and oxidative stress are important pathological mechanisms following traumatic brain injury (TBI). The NF-κB/COX2 pathway regulates neuroinflammation and oxidative damage, while microglia also play an important role in neuroinflammation. Since NF-κB is involved in microglial polarization, targeting this pathway and microglial polarization is a critical component of TBI treatment. Currently, electroacupuncture (EA) is widely used to treat various symptoms after TBI, but the mechanisms of EA remain poorly understood. Additionally, the optimal frequency of EA remains unclear, which affects its efficacy. This study focuses on exploring the optimal frequency parameters of EA on TBI and investigating the underlying mechanisms of EA through NF-κB/COX2 pathway and microglial polarization. METHODS: The study was divided into two parts. In Experiment 1, 42 Sprague Dawley (SD) rats were induced and randomly divided into seven groups (n = 6). Except for the sham group, all rats underwent controlled cortical impact (CCI) to establish TBI model. Four EA groups (with different frequencies) and manual acupuncture (without current stimulation) received stimulation on the acupoints of Shuigou (GV26), Fengchi (GB20) and Neiguan (PC6) once a day for 7 days. The neurological function was assessed by modified Neurological Severity Scores (mNSS), and the rats' memory and learning were examined by the Morris water maze (MWM). SOD, MDA, and GSH-Px were detected to evaluate the levels of oxidative stress. The levels of IL-1ß, IL-6, and TNF-α were evaluated by Enzyme Linked Immunosorbent Assay (ELISA). Detection of the above indicators indicated a treatment group that exerted the strongest neuroprotection against TBI, we then conducted Experiment 2 using this screened acupuncture treatment to investigate the mechanism of acupuncture. 48 rats were randomly divided into four groups (n = 12): sham, TBI model, acupuncture and PDTC (NF-κB inhibitor). Evaluations of mNSS, MWM test, SOD, MDA, GSH-Px, IL-1ß, IL-6, TNF-α, and IL-10 were the same as in Experiment 1. Western blot was applied for detecting the expression levels of NF-κB, p-NF-κB, COX2, and Arg-1. TUNEL was used to examine neuronal apoptosis. Brain structure was observed by H&E. Iba-1, COX2, and Arg-1 were investigated by immunofluorescence staining. RESULTS: EA with frequency of 2/100 Hz markedly improved neuronal and cognitive function as compared to the other treatment groups. Moreover, it downregulated the expression of MDA, IL-6, IL-1ß, and TNF-α and upregulated the levels of SOD and GSH-Px. In addition, Both EA with 2/100 Hz and PDTC reduced the levels of p-NF-κB, COX2 and M1 markers (COX2, IL-6, IL-1ß, TNF-α) and increased the levels of M2 markers (Arg-1, IL-10). Moreover, they had similar effects on reducing inflammation, oxidative stress and apoptosis, and improving neuronal and cognitive function. CONCLUSIONS: The collective findings strongly suggest that EA with 2/100 Hz can improve neurologic function by suppressing neuroinflammation, oxidative stress and apoptosis. Additionally, we confirm that EA promotes microglial polarization towards the M2 phenotype through the suppression of NF-κB/COX2 pathway, thus exerting neuroprotective effects after TBI.
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Lesiones Traumáticas del Encéfalo , Ciclooxigenasa 2 , Electroacupuntura , Microglía , Neuroprotección , Animales , Ratas , Lesiones Traumáticas del Encéfalo/genética , Lesiones Traumáticas del Encéfalo/metabolismo , Lesiones Traumáticas del Encéfalo/terapia , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/metabolismo , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Microglía/metabolismo , Enfermedades Neuroinflamatorias , FN-kappa B/metabolismo , Ratas Sprague-Dawley , Superóxido Dismutasa/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Modelos Animales de Enfermedad , Estrés Oxidativo , ApoptosisRESUMEN
Viburnum luzonicum Rolfe is widely used in China as folk medicine. The bioactivity evaluation indicated that the n-BuOH fraction of V. luzonicum leaves (VLLB) could significantly inhibit αamylase and α-glucosidase. In order to clarify its active constituents, the phytochemical analysis on VLLB was first performed using HPLC-QTOF-MS/MS, and three new phenolic compounds, viburosides A-C (1-3), along with seven known analogues (4-10) were isolated through preparative HPLC. The undescribed compounds were determined by extensive spectroscopic analyses (1H and 13C NMR, HSQC, HMBC, HRESIMS, and ORD) and enzymatic hydrolysis. In the in vitro enzyme assays, compounds 1-8 showed potent αamylase and α-glucosidase inhibitory activities. The enzymatic kinetics and molecular docking of the strongest inhibitors 2 and 3 against the corresponding target enzyme were also performed.
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Background: This study is aimed at investigating whether relaxin-3 exhibits protective effects against cardiomyopathy in diabetic rats by suppressing ERS. Methods: Eighty male SD rats were randomly divided into two groups: controls (n = 20) and diabetes (n = 60). The streptozotocin-treated rats were randomly divided into three groups: diabetic group (DM), low-dose relaxin-3 group (0.2 µg/kg/d), and high-dose relaxin-3 group (2 µg/kg/d). The myocardial tissues and collagen fiber were observed by hematoxylin and eosin (H&E) and Masson staining. Serum brain natriuretic peptide (BNP), troponin (TNI), myoglobin, interleukin (IL-17), interleukin (IL)-1α, and tumor necrosis factor (TNF)-α were determined by ELISA. The protein expression of glucose regulatory protein 78 (GRP78) and C/EBP homologous protein (CHOP) in the heart tissue of each group was detected by Western blot analysis. Results: (1) HE and Masson staining indicated that relaxin-3 could attenuate myocardial lesions and myocardial collagen volume fraction. (2) BNP, TnI, and myoglobin in the DM group at four and eight weeks were significantly higher than in the controls (P < 0.01). The relaxin-3-treated groups showed significantly reduced serum BNP, TnI, and myoglobin levels compared with the DM group (P < 0.05). (3) IL-17, IL-1α, and TNF-α levels in the DM rats at 4 weeks were higher than in the controls (P < 0.05). Low or high dose of relaxin-3-treated groups showed reduced serum IL-17 and TNF-α levels compared with the DM group at four and eight weeks (P < 0.05). (4) CHOP and GRP78 protein expression was increased in the DM group at four and eight weeks compared with the controls (P < 0.01), and small and large doses of relaxin-3 significantly reduced GRP78 and CHOP protein expression. Conclusions: Exogenous relaxin-3 ameliorates diabetic cardiomyopathy by inhibiting ERS in diabetic rats.
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Diabetes Mellitus Experimental , Cardiomiopatías Diabéticas , Relaxina , Animales , Apoptosis , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Cardiomiopatías Diabéticas/tratamiento farmacológico , Cardiomiopatías Diabéticas/patología , Estrés del Retículo Endoplásmico , Eosina Amarillenta-(YS)/farmacología , Eosina Amarillenta-(YS)/uso terapéutico , Glucosa , Hematoxilina/farmacología , Hematoxilina/uso terapéutico , Interleucina-17/farmacología , Interleucina-17/uso terapéutico , Masculino , Mioglobina/farmacología , Mioglobina/uso terapéutico , Péptido Natriurético Encefálico/farmacología , Péptido Natriurético Encefálico/uso terapéutico , Ratas , Ratas Sprague-Dawley , Relaxina/farmacología , Relaxina/uso terapéutico , Estreptozocina/farmacología , Estreptozocina/uso terapéutico , Troponina/farmacología , Troponina/uso terapéutico , Factor de Necrosis Tumoral alfaRESUMEN
BACKGROUND: High-dose dexamethasone is the standard initial treatment for patients with immune thrombocytopenia, but many patients still relapse and require further treatments. All-trans retinoic acid has been shown to exert immunomodulatory effects and promote thrombopoiesis, and so we aimed to assess the activity and safety of all-trans retinoic acid plus high-dose dexamethasone as a first-line treatment for newly diagnosed patients with immune thrombocytopenia. METHODS: This multicentre, open-label, randomised, controlled, phase 2 trial was done at six different tertiary medical centres in China. Eligible participants were adults (aged >18 years) with treatment-naive, newly diagnosed, primary immune thrombocytopenia who had either a platelet count of less than 30â×â109 platelets per L or a platelet count of less than 50â×â109 platelets per L and clinically significant bleeding. We randomly assigned (1:1) participants to receive either all-trans retinoic acid (10 mg orally twice daily for 12 weeks) plus high-dose dexamethasone (40 mg/day intravenously for 4 consecutive days) or high-dose dexamethasone alone using a central, web-based randomisation system. If patients did not respond by day 14, the 4-day course of dexamethasone was repeated. The primary endpoint was 6-month sustained response, defined as the maintenance of a platelet count of at least 30â×â109 platelets per L and at least 2-times higher than the baseline count and the absence of bleeding, with no need for rescue medication at this time. The primary endpoint was analysed by intention-to-treat and safety was assessed in all participants who received at least one dose of the study drug. This trial is registered with ClinicalTrials.gov, NCT04217148, and is now completed. FINDINGS: Between Jan 1, 2020, and June 30, 2020, 132 patients were randomly assigned to either all-trans retinoic acid plus high-dose dexamethasone (n=66) or high-dose dexamethasone alone (n=66). Three patients did not receive their allocated treatment, leaving 129 in the safety analysis set. At 6 months, a significantly higher proportion of participants in the all-trans retinoic acid plus high-dose dexamethasone group (45 [68%] of 66) than in the high-dose dexamethasone monotherapy group (27 [41%] of 66) had a sustained response (OR 3·095, 95% CI 1·516-6·318; p=0·0017). The most common adverse events were dry skin (31 [48%] of 64 patients), headaches (12 [19%]), and insomnia (12 [19%]) in the combination group, and insomnia (ten [15%] of 65 patients) and anxiety or mood disorders (eight [12%]) in the monotherapy group. Both treatments were well tolerated and no grade 4 or worse adverse events occurred. There were no treatment-related deaths. INTERPRETATION: The combination of all-trans retinoic acid and high-dose dexamethasone was safe and active in newly diagnosed patients with primary immune thrombocytopenia, providing a sustained response. This regimen represents a potential first-line treatment in this setting, but further studies are needed to validate its efficacy and safety. FUNDING: The Beijing Municipal Science and Technology Commission, the National Natural Science Foundation of China, the Beijing Natural Science Foundation, the National Key Research and Development Program of China, and the Foundation for Innovative Research Groups of the National Natural Science Foundation of China.
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Dexametasona/uso terapéutico , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Tretinoina/uso terapéutico , Adulto , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Femenino , Humanos , Masculino , Púrpura Trombocitopénica Idiopática/diagnóstico , Resultado del TratamientoRESUMEN
BACKGROUND: Acupuncture is widely used for pain diseases while evidence of its efficacy for sciatica is insufficient. We aim to explore the feasibility and efficacy of acupuncture with different acupoint selecting strategies for sciatica induced by lumbar disc herniation. METHODS: This is a multicenter, three-arm, patient-assessor-blinded randomized controlled pilot trial. Ninety patients will be assigned randomly into 3 groups including disease-affected meridians (DAM) group, non-affected meridians (NAM) group, and sham acupuncture (SA) group in a 1:1:1 ratio. The trial involves a 4-week treatment along with follow-up for 22 weeks. The primary outcome is the change of leg pain intensity measured by the visual analogue scale (VAS) from baseline to week 4 after randomization. Secondary outcomes include functional status, back pain intensity, and quality of life. Adverse events will also be recorded. DISCUSSION: The results will inspire the optimal acupuncture strategy for sciatica and help establish a better design as well as power calculation for a full-scale study. TRIAL REGISTRATION: ChiCTR2000030680 (Chinese Clinical Trial Registry, http://www.chictr.org.cn , registered on 9 March 2020).
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Terapia por Acupuntura , Ciática , Terapia por Acupuntura/efectos adversos , Humanos , Estudios Multicéntricos como Asunto , Proyectos Piloto , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Ciática/diagnóstico , Ciática/terapia , Factores de Tiempo , Resultado del TratamientoRESUMEN
Eight previously undescribed lignan glycosides, viburmacrosides A-H (1-8), and seven known analogues (9-15) were isolated from Viburnum macrocephalum f. keteleeri fruits through bioactivity-guided fractionation. Their structures and absolute configurations were elucidated by extensive spectroscopic analyses and chemical evidence. Using the well-recognized carbohydrate-hydrolyzing enzymes α-amylase and α-glucosidase, as well as the promising protein tyrosine phosphatase 1B (PTP1B), as inhibitory targets, all isolated compounds were tested for their antidiabetic potential in vitro. Compound 4 displayed potent inhibitory activities with IC50 values of 9.9 ± 0.6 and 8.9 ± 0.5 µM against α-glucosidase and PTP1B, respectively. The enzymatic kinetics results suggested that compound 4 competitively inhibited α-glucosidase while it suppressed α-amylase and PTP1B in the mixed-type manner. These findings supported that V. macrocephalum f. keteleeri fruits may be a new functional food resource with antidiabetic potential.
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Inhibidores Enzimáticos/química , Lignanos/química , Extractos Vegetales/química , Proteína Tirosina Fosfatasa no Receptora Tipo 1/antagonistas & inhibidores , Viburnum/química , alfa-Amilasas/antagonistas & inhibidores , Frutas/química , Inhibidores de Glicósido Hidrolasas/química , Humanos , Hipoglucemiantes/química , Cinética , Estructura Molecular , Proteína Tirosina Fosfatasa no Receptora Tipo 1/química , alfa-Amilasas/química , alfa-Glucosidasas/químicaRESUMEN
Appropriate producing areas can guarantee the quality of Tibetan medicine, but research on the suitable ecological factors and suitable producing areas of Tibetan medicinal plants is scarce. This paper used the Geographic Information System for Global Medicinal Plants(GMPGIS) to analyze the ecological suitability of Tibetan medicinal plants nationwide. For the first time, the range of ecological factors and main soil types of Tibetan medicinal plants were extracted, such as the average annual temperature-19.4-24.2 â, annual average precipitation 17-4 088 mm, annual average sunshine 124.2-171.6 W·m~(-2). The main soil types were black calcareous soil, thin layer soil, chestnut soil and so on. Based on 337 sampling points, the largest ecological similarity area of Tibetan medicine across the country was obtained through ecological similarity analysis. In addition to Tibet and Qinghai provinces and Tibetan Autonomous Prefectures in Sichuan, Gansu, and Yunnan provinces, Jiuquan city and Linxia county in Gansu province, Panzhihua and Ya'an in Sichuan province, and Xinjiang, Inner Mongolia, and Shanxi provinces also had larger suitable cultivation areas. In addition, by analyzing the current situation of Tibetan medicine industry, the research pointed out that there were some problems such as unreasonable development and utilization of resources, lack of standards and norms, weak basic research and imperfect industrial system, and made corresponding countermeasures for sustainable development of resources, formulation of standards and specifications, promotion of medicine through science and technology, expansion of domestic and foreign markets, etc. This study provided the basis for guiding the rational layout of production bases, introduction and breeding of plant Tibetan medicine nationwide, laying the foundation for the scientific and standardized production of high-quality Tibetan medicine, clarifying the development direction of Tibetan medicine industry, and providing ideas for the development strategy of Tibetan medicine and other national medicine industry.
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Desarrollo Industrial , Medicina Tradicional Tibetana , China , Suelo , TibetRESUMEN
The study aimed to investigate the multi-constituent, multi-target mechanism of Xuanfei Baidu Tang(XFBD) in the treatment of coronavirus disease 2019(COVID-19), through exploring the main ingredients and effective targets of XFBD, as well as analyzing the correlation between XFBD targets and COVID-19. The compounds of each herb in XFBD were collected from TCM-PTD, ETCM, TCMSP and SymMap database. Next, the information of meridian tropisms was collected from Chinese Pharmacopoeia(2015 edition), and the target information of the major constituents of XFBD were obtained from TCM-PTD, ETCM, TCMSP and TargetNet database. Subsequently, the target network model and the major modules were generated by Cytoscape, and the functional enrichment analysis of XFBD targets were completed by DAVID and STRING. As a result, ten of the 13 herbs in XFBD belonged to the lung meridian, and 326 of the 1 224 putative XFBD targets were associated with the disease target of COVID-19, among which 109 targets were enriched in the disease pathways of viral infection and lung injury. The main biological pathways regulated by the key XFBD targets included viral infection, energy metabolism, immunity and inflammation, parasites and bacterial infections. In conclusion, the therapeutic mechanism of XFBD in COVID-19 showed a multi-herb, multi-constituent, multi-target pattern, with lung as the chief targeted organ. By regulating a series of biological pathways closely related to the occurrence and development of diseases, XFBD plays a role in balancing immunity, eliminating inflammation, regulating hepatic and biliary metabolism and recovering energy metabolism balance.
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Betacoronavirus , Infecciones por Coronavirus , Medicamentos Herbarios Chinos/uso terapéutico , Pandemias , Neumonía Viral , COVID-19 , Infecciones por Coronavirus/tratamiento farmacológico , Humanos , Medicina Tradicional China , Neumonía Viral/tratamiento farmacológico , SARS-CoV-2 , Tratamiento Farmacológico de COVID-19RESUMEN
BACKGROUND: Endothelial cells (ECs) function as an instructive platform to support haematopoietic stem cell (HSC) homeostasis. Our recent studies found that impaired bone marrow (BM) ECs are responsible for the defective haematopoiesis in patients with poor graft function (PGF), which is characterised by pancytopenia post-allotransplant. Although activated autophagy was reported to benefit ECs, whether EC autophagy plays a critical role in supporting HSCs and its effect on PGF patients post-allotransplant remain unclear. METHODS: To evaluate whether the autophagy status of ECs modulates their ability to support haematopoiesis, human umbilical vein endothelial cells (HUVECs) and primary BM ECs derived from healthy donors were subjected to knockdown or overexpression of Beclin-1 (an autophagy-related protein). Moreover, BM ECs derived from PGF patients were studied. FINDINGS: Beclin-1 knockdown significantly reduced the haematopoiesis-supporting ability of ECs by suppressing autophagy, which could be restored by activating autophagy via Beclin-1 upregulation. Moreover, autophagy positively regulated haematopoiesis-related genes in HUVECs. Subsequently, a prospective case-control study demonstrated that defective autophagy reduced Beclin-1 expression and the colony-forming unit (CFU) plating efficiency in BM ECs from PGF patients compared to matched patients with good graft function. Rapamycin, an autophagy activator, quantitatively and functionally improved BM ECs from PGF patients in vitro and enhanced their ability to support HSCs by activating the Beclin-1 pathway. INTERPRETATION: Our results suggest that the autophagy status of ECs modulates their ability to support haematopoiesis by regulating the Beclin-1 pathway. Defective autophagy in BM ECs may be involved in the pathogenesis of PGF post-allotransplant. Rapamycin provides a promising therapeutic approach for PGF patients. FUNDING: Please see funding sources.
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Autofagia , Endotelio Vascular/metabolismo , Hematopoyesis , Pancitopenia/metabolismo , Beclina-1/genética , Beclina-1/metabolismo , Transfusión de Sangre Autóloga/efectos adversos , Células Cultivadas , Endotelio Vascular/citología , Células Madre Hematopoyéticas/citología , Células Madre Hematopoyéticas/metabolismo , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Monocitos/citología , Monocitos/metabolismo , Pancitopenia/etiologíaRESUMEN
Mast cells and basophils are multifunctional effector cells that contain abundant secretory granules in their cytoplasm. Both cell types are involved in a variety of inflammatory and immune events, producing an array of inflammatory mediators, such as cytokines. The aim of the study was to examine whether isoquercitrin modulates allergic and inflammatory reactions in the human basophilic KU812 cells and to elucidate its influence on the phosphorylation of mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB activation. The KU812 cells were stimulated with phorbol-12-myristate 13-acetate plus the calcium ionophore A23187 (PMACI). The inhibitory effects of isoquercitrin on the productions of histamine and pro-inflammatory cytokines in the stimulated KU812 cells were measured using cytokine-specific enzyme-linked immunosorbent (ELISA) assays. Western blotting analysis was used to assess the effects of isoquercitrin on the MAPKs and NF-κB protein levels. Our results indicated that the isoquercitrin treatment of PMACI-stimulated KU812 cells significantly reduced the production of histamine and the pro-inflammatory cytokines, such as interleukin (IL)-6, IL-8, IL-1ß, and tumor necrosis factor (TNF)-α. The treated cells exhibited decreased phosphorylation of extracellular signal-regulated kinase (ERK), revealing the role of ERK MAPK in isoquercitrin-mediated allergy inhibition. Furthermore, isoquercitrin suppressed the PMACI-mediated activation of NF-κB in the human basophil cells. In conclusion, the results from the present study provide insights into the potential therapeutic use of isoquercitrin for the treatment of inflammatory and allergic reactions.
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Citocinas/inmunología , Quinasas MAP Reguladas por Señal Extracelular/inmunología , Histamina/inmunología , Hipersensibilidad/inmunología , FN-kappa B/inmunología , Quercetina/análogos & derivados , Basófilos/efectos de los fármacos , Basófilos/inmunología , Citocinas/genética , Regulación hacia Abajo/efectos de los fármacos , Quinasas MAP Reguladas por Señal Extracelular/genética , Humanos , Hipersensibilidad/tratamiento farmacológico , Hipersensibilidad/genética , FN-kappa B/genética , Quercetina/farmacologíaRESUMEN
This study investigated the prognostic factors and clinical outcomes of preemptive chemotherapy followed by granulocyte colony-stimulating factor-primed donor leukocyte infusion (Chemo-DLI) according to minimal residual disease (MRD) status in patients with acute leukemia and myelodysplastic syndromes who received allogeneic hematopoietic stem cell transplantation (HSCT) (n = 101). Patients received immunosuppressive drugs to prevent graft-vs.-host disease (GVHD) after Chemo-DLI. The 3-yr cumulative incidences of relapse, non-relapse mortality, and disease-free survival (DFS) after HSCT were 39.5%, 9.6%, and 51.7%, respectively. The cumulative incidences of relapse and DFS were significantly poorer in patients who exhibited early-onset MRD. Forty-four patients turned MRD negative 1 month after Chemo-DLI; their cumulative incidences of relapse and DFS were significantly better than those with persistent MRD 1 month after preemptive Chemo-DLI (relapse: 19.8% vs. 46.8%, P = 0.001; DFS: 69.6% vs. 46.4%, P = 0.004). The cumulative incidences of relapse and DFS after HSCT were significantly better in patients with chronic GVHD (cGVHD) than those without cGVHD (relapse: 19.6% vs. 63.7%, P < 0.001; DFS: 74.4% vs. 23.8%, P < 0.001). Early-onset MRD, persistent MRD after Chemo-DLI, and non-cGVHD after Chemo-DLI, which were associated with increased relapse and impaired DFS, suggest unsatisfactory response to preemptive Chemo-DLI.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Enfermedad Injerto contra Huésped/prevención & control , Leucemia/terapia , Transfusión de Leucocitos , Síndromes Mielodisplásicos/terapia , Enfermedad Aguda , Adolescente , Adulto , Transfusión de Sangre Autóloga , Niño , Preescolar , Femenino , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Antígenos HLA/genética , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Leucemia/diagnóstico , Leucemia/mortalidad , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/diagnóstico , Síndromes Mielodisplásicos/mortalidad , Neoplasia Residual/diagnóstico , Pronóstico , Recurrencia , Terapia Recuperativa , Análisis de Supervivencia , Acondicionamiento Pretrasplante , Trasplante Homólogo , Resultado del Tratamiento , Adulto JovenRESUMEN
The present study was designed to determine the effects of a traditional Chinese medicine, called Qishen Yiqi Dropping Pill on chronic hypoxia-induced myocardial injury. To establish a rat chronic hypoxia model to be used in the evaluation of the therapeutic effects of the Qishen Yiqi Dropping Pill, Sprague-Dawley (SD) rats were randomly divided into three groups: the control, model, and treatment groups (n = 10 per group). The animals were housed in a plexiglass container. The control animals were under normal oxygen concentration and the model and treatment groups were exposed to air and nitrogen for 5 weeks. The rats in the treatment group were orally administered the Qishen Yiqi Dropping pill (35 mg·kg(-1)·d(-1)) for 5 weeks. After the treatment, the cardiac function and morphology were analyzed, and the expression levels of hypoxia-inducible factor 1α (HIF-1α) were determined using Western blotting. Our results indicated that the cardiac function was impaired, cell apoptosis was enhanced, and HIF-1α expression was up-regulated in the model group, compared to the control group. These changes were ameliorated by the treatment with the Qishen Yiqi Dropping Pill. In conclusion, Qishen Yiqi Dropping pill can ameliorate myocardial injury induced by chronic hypoxia, improve cardiac function, and decrease myocardial cell apoptosis, which may provide a basis for its clinical use for the treatment of chronic cardiovascular diseases.
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Cardiomiopatías/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Corazón/efectos de los fármacos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Miocardio , Oxígeno/metabolismo , Fitoterapia , Animales , Apoptosis , Cardiomiopatías/etiología , Cardiomiopatías/metabolismo , Cardiomiopatías/patología , Medicamentos Herbarios Chinos/farmacología , Corazón/fisiopatología , Hipoxia , Miocardio/metabolismo , Miocardio/patología , Ratas Sprague-DawleyRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Wenshen Zhuanggu Formula (WSZG), a traditional Chinese medicine (TCM) empirical prescription, has been used to treat the patients with breast cancer bone metastasis as an adjuvant in clinical practice. To explore the anti-metastatic activity and potential mechanisms of WSZG-containing serum (WSZG-CS) on highly bone-metastatic human breast cancer MDA-MB-231BO cells. MATERIALS AND METHODS: MDA-MB-231BO cells were cultured alone or co-cultured with bone marrow-derived mesenchymal stem cells (BMSCs). Invasion assays were carried out in Matrigel-coated Transwell chambers. CC chemokine 5 (CCL5) and interleukin (IL)-17B secretion levels were detected by ELISA. CCR5 and IL-17BR protein expression levels were determined by immunocytochemistry and Western blot analysis. RESULTS: Compared with control serum, WSZG-CS significantly inhibited BMSC induced MDA-MB-231BO breast cancer cell invasion, reduced CCL5 and IL-17B levels in co-culture supernatants, and downregulated CCR5 and IL-17BR protein expression in breast cancer cells co-cultured with BMSCs. CONCLUSIONS: WSZG-CS exerts an anti-metastatic activity against MDA-MB-231BO breast cancer cells, due to its ability to mitigate the interaction between BMSCs and breast cancer cells mediated via the CCL5/CCR5 and IL-17B/IL-17BR signaling pathways.
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Antineoplásicos/farmacología , Neoplasias de la Mama/metabolismo , Extractos Vegetales/farmacología , Animales , Línea Celular , Línea Celular Tumoral , Quimiocina CCL5/metabolismo , Técnicas de Cocultivo , Cumarinas/análisis , Femenino , Ficusina/análisis , Furocumarinas/análisis , Humanos , Interleucina-17/metabolismo , Masculino , Medicina Tradicional China , Células Madre Mesenquimatosas/metabolismo , Extractos Vegetales/química , Ratas Sprague-Dawley , SueroRESUMEN
The hypoglycemic and antioxidant effects of the water extract from Anoectochilus roxburghii in alloxan-induced diabetic mice were examined. Compared with untreated diabetic mice, the daily oral administration of the water extract from A. roxburghii at 0.5 or 2 g/kg for 14 days caused a significant decrease (p<.05) in blood glucose levels with similar effect but no evidence of dose-related effect. Simultaneously, the alteration in lipid metabolism was partially attenuated as evidenced by decreased serum total cholesterol and triglyceride levels and by increased high-density lipoprotein cholesterol concentration in diabetic mice (p<.05) but no dose-related effect was observed. In addition, the water extract from A. roxburghii caused a significant increase (p<.05) in the activities of enzymic antioxidants and the levels of vitamin E in liver and kidney of diabetic mice. Our results suggest that water extract from A. roxburghii possesses hypoglycemic and antioxidant properties after oral administration to mice showing alloxan-induced diabetes.
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Antioxidantes/uso terapéutico , Diabetes Mellitus Experimental/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Hipoglucemiantes/uso terapéutico , Orchidaceae/química , Aloxano/farmacología , Animales , Antioxidantes/administración & dosificación , Antioxidantes/aislamiento & purificación , Antioxidantes/farmacología , Glucemia/análisis , Relación Dosis-Respuesta a Droga , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/aislamiento & purificación , Medicamentos Herbarios Chinos/farmacología , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/aislamiento & purificación , Hipoglucemiantes/farmacología , Riñón/efectos de los fármacos , Riñón/enzimología , Metabolismo de los Lípidos/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/enzimología , Masculino , Ratones , Ratones EndogámicosRESUMEN
Cigarette smoke creates a molecular field of injury in epithelial cells that line the respiratory tract. We hypothesized that transcriptome sequencing (RNA-Seq) will enhance our understanding of the field of molecular injury in response to tobacco smoke exposure and lung cancer pathogenesis by identifying gene expression differences not interrogated or accurately measured by microarrays. We sequenced the high-molecular-weight fraction of total RNA (>200 nt) from pooled bronchial airway epithelial cell brushings (n = 3 patients per pool) obtained during bronchoscopy from healthy never smoker (NS) and current smoker (S) volunteers and smokers with (C) and without (NC) lung cancer undergoing lung nodule resection surgery. RNA-Seq libraries were prepared using 2 distinct approaches, one capable of capturing non-polyadenylated RNA (the prototype NuGEN Ovation RNA-Seq protocol) and the other designed to measure only polyadenylated RNA (the standard Illumina mRNA-Seq protocol) followed by sequencing generating approximately 29 million 36 nt reads per pool and approximately 22 million 75 nt paired-end reads per pool, respectively. The NuGEN protocol captured additional transcripts not detected by the Illumina protocol at the expense of reduced coverage of polyadenylated transcripts, while longer read lengths and a paired-end sequencing strategy significantly improved the number of reads that could be aligned to the genome. The aligned reads derived from the two complementary protocols were used to define the compendium of genes expressed in the airway epithelium (n = 20,573 genes). Pathways related to the metabolism of xenobiotics by cytochrome P450, retinol metabolism, and oxidoreductase activity were enriched among genes differentially expressed in smokers, whereas chemokine signaling pathways, cytokine-cytokine receptor interactions, and cell adhesion molecules were enriched among genes differentially expressed in smokers with lung cancer. There was a significant correlation between the RNA-Seq gene expression data and Affymetrix microarray data generated from the same samples (P < 0.001); however, the RNA-Seq data detected additional smoking- and cancer-related transcripts whose expression was were either not interrogated by or was not found to be significantly altered when using microarrays, including smoking-related changes in the inflammatory genes S100A8 and S100A9 and cancer-related changes in MUC5AC and secretoglobin (SCGB3A1). Quantitative real-time PCR confirmed differential expression of select genes and non-coding RNAs within individual samples. These results demonstrate that transcriptome sequencing has the potential to provide new insights into the biology of the airway field of injury associated with smoking and lung cancer. The measurement of both coding and non-coding transcripts by RNA-Seq has the potential to help elucidate mechanisms of response to tobacco smoke and to identify additional biomarkers of lung cancer risk and novel targets for chemoprevention.
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Biomarcadores de Tumor/genética , Perfilación de la Expresión Génica , Neoplasias Pulmonares/etiología , ARN Mensajero/genética , Fumar/efectos adversos , Bronquios/citología , Bronquios/efectos de los fármacos , Bronquios/metabolismo , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Células Epiteliales/patología , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Análisis de Secuencia por Matrices de Oligonucleótidos , ARN Neoplásico/genética , Mucosa Respiratoria/citología , Mucosa Respiratoria/efectos de los fármacos , Mucosa Respiratoria/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Five new phenylpropanoids, named balajaponins A-E (1-5), were isolated from Balanophora japonica, along with 24 known compounds. Among them, three hydrolysable tannins (6-8) showed specific in vitro α-glucosidase inhibition, with IC50 values in the range of 1-4 µM. Kinetic analysis revealed that they all acted in a noncompetitive mode.
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Balanophoraceae/química , Inhibidores de Glicósido Hidrolasas , Taninos Hidrolizables/farmacología , Fenilpropionatos/farmacología , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Taninos Hidrolizables/química , Concentración 50 Inhibidora , Cinética , Espectroscopía de Resonancia Magnética , Estructura Molecular , Fenilpropionatos/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , alfa-Glucosidasas/metabolismoRESUMEN
B-type natriuretic peptide (BNP) has been known to be secreted from cardiac myocytes and activate its receptor, natriuretic peptide receptor-A (NPR-A), to reduce ventricular fibrosis. However, the function of BNP/NPR-A pathway in the somatic sensory system has been unknown. In the present study, we report a novel function of BNP in pain modulation. Using microarray and immunoblot analyses, we found that BNP and NPR-A were expressed in the dorsal root ganglion (DRG) of rats and upregulated after intraplantar injection of complete Freund's adjuvant (CFA). Immunohistochemistry showed that BNP was expressed in calcitonin gene-related peptide (CGRP)-containing small neurons and IB4 (isolectin B4)-positive neurons, whereas NPR-A was present in CGRP-containing neurons. Application of BNP reduced the firing frequency of small DRG neurons in the presence of glutamate through opening large-conductance Ca2+-activated K+ channels (BKCa channels). Furthermore, intrathecal injection of BNP yielded inhibitory effects on formalin-induced flinching behavior and CFA-induced thermal hyperalgesia in rats. Blockade of BNP signaling by BNP antibodies or cGMP-dependent protein kinase (PKG) inhibitor KT5823 [(9S,10R,12R)-2,3,9,10,11,12-hexahydro-10-methoxy-2,9-dimethyl-1-oxo-9,12-epoxy-1H-diindolo[1,2,3-fg:3',2',1'-kl]pyrrolo[3,4-i][1,6]benzodiazocine-10-carboxylic acid methyl ester] impaired the recovery from CFA-induced thermal hyperalgesia. Thus, BNP negatively regulates nociceptive transmission through presynaptic receptor NPR-A, and activation of the BNP/NPR-A/PKG/BKCa channel pathway in nociceptive afferent neurons could be a potential strategy for inflammatory pain therapy.
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Regulación de la Expresión Génica/fisiología , Péptido Natriurético Encefálico/metabolismo , Dolor/metabolismo , Células Receptoras Sensoriales/metabolismo , Transducción de Señal/fisiología , Análisis de Varianza , Animales , Anticuerpos/farmacología , Anticuerpos/uso terapéutico , Fenómenos Biofísicos/efectos de los fármacos , Fenómenos Biofísicos/fisiología , Péptido Relacionado con Gen de Calcitonina/metabolismo , Carbazoles/farmacología , Carbazoles/uso terapéutico , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/uso terapéutico , Potenciales Postsinápticos Excitadores/efectos de los fármacos , Adyuvante de Freund , Ganglios Espinales/patología , Regulación de la Expresión Génica/efectos de los fármacos , Ácido Glutámico/farmacología , Hiperalgesia/complicaciones , Hiperalgesia/tratamiento farmacológico , Inflamación/inducido químicamente , Inflamación/complicaciones , Lectinas/metabolismo , Masculino , Potenciales de la Membrana/efectos de los fármacos , Potenciales de la Membrana/fisiología , Péptido Natriurético Encefálico/inmunología , Dolor/tratamiento farmacológico , Dolor/etiología , Dimensión del Dolor/métodos , Técnicas de Placa-Clamp/métodos , Péptidos/farmacología , Ratas , Ratas Sprague-Dawley , Receptores del Factor Natriurético Atrial/metabolismo , Células Receptoras Sensoriales/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Factores de TiempoRESUMEN
This paper is aimed to develop a rapid and sensitive HPLC-fluorescence detection (FLD) method for the determination of tetrahydropalmatine (TET) in rats' plasma. The influence of combinations of Extractum Angelicae Dahuricae Siccum (coumarin and volatile oil) and total alkaloids (TA) from Rhizoma Corydalis (TA) on pharmacokinetics of TET in rats was studied. Plasma samples were treated with hexane-isopropanol (95:5) to precipitate the protein, and were determined by HPLC-fluorescence detection. The calibration curve was linear in the range of 2.096-167.68 microg L(-1). The limit of quantification was 2.096 microg L(-1). The method recovery of TET was 94.0%-100.0%. The extract recovery was 72.0%-81.5%. RSDs ofintra- and inter-day precisions were all less than 7.0%. Pharmacokinetics of TET in rats was fitted to two compartments open model after oral administration of TA, TA-volatile oil (VO), TA-coumarin (Cou) and TA-VO-Cou. Compared with TA, AUC(0-t), AUC(0-infinity), MRT(0-t), and MRT(0-infinity) of TET had significant deviation when combined with VO and/or Cou. The determination method is sensitive, specific, accurate, and appropriate for determination of TET in vivo. Coumarin and/or VO combined with TA can prolong the resistance time of TET significantly, delay elimination and enhance bioavailability of tetrahydropalmatine.
Asunto(s)
Alcaloides/farmacología , Alcaloides de Berberina/farmacocinética , Medicamentos Herbarios Chinos/farmacología , Alcaloides/administración & dosificación , Angelica/química , Animales , Corydalis/química , Cumarinas/administración & dosificación , Cumarinas/farmacología , Medicamentos Herbarios Chinos/administración & dosificación , Aceites Volátiles/administración & dosificación , Aceites Volátiles/farmacología , Ratas , Ratas Sprague-Dawley , Rizoma/químicaRESUMEN
Two new labdane-type diterpenoids vitetrifolin H (1) and vitetrifolin I (2), and one new monoterpenoid vitexoid (3), were isolated from the fruits of Vitex trifolia L., together with seven known diterpenoids. Structures of all compounds were elucidated by extensive spectroscopic methods. All these compounds exhibited inhibition of Hela cell proliferation, with IC50 values in the range of 4-28 microM. In addition, vitetrifolin I (2) induced cell cycle G0/G1 phase arrest and apoptosis of Hela cells.