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Currently, natural products are one of the priceless options for finding novel chemical pharmaceutical entities. Ellipticine is a naturally occurring alkaloid isolated from the leaves of Ochrosia elliptica Labill. Ellipticine and its derivatives are characterized by multiple biological activities. The purpose of this review was to provide a critical and systematic assessment of ellipticine and its derivatives as bioactive molecules over the last 60â years. Publications focused mainly on the total synthesis of alkaloids of this type without any evaluation of bioactivity have been excluded. We have reviewed papers dealing with the synthesis, bioactivity evaluation and mechanism of action of ellipticine and its derivatives. It was found that ellipticine and its derivatives showed cytotoxicity, antimicrobial ability, and anti-inflammatory activity, among which cytotoxicity toward cancer cell lines was the most investigated aspect. The inhibition of DNA topoisomerase II was the most relevant mechanism for cytotoxicity. The PI3K/AKT pathway, p53 pathway, and MAPK pathway were also closely related to the antiproliferative ability of these compounds. In addition, the structure-activity relationship was deduced, and future prospects were outlined. We are confident that these findings will lay a scientific foundation for ellipticine-based drug development, especially for anticancer agents.
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Elipticinas , Elipticinas/farmacología , Elipticinas/química , Humanos , Relación Estructura-Actividad , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Proliferación Celular/efectos de los fármacos , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinfecciosos/farmacología , Antiinfecciosos/química , Estructura Molecular , Animales , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificaciónRESUMEN
Natural products are treasure houses for modern drug discovery. Diphyllin is a natural arylnaphthalene lignan lactone isolated from the leaf of Astilboides tabularis. Studies have found that it possesses plenty of bioactivity characteristics. In this paper, we reviewed the structure, bioactivity, and mechanism of action of diphyllin and its derivatives. The references were obtained from PubMed, Web of Science, and Science Direct databases up to August 2023. Papers without a bio-evaluation were excluded. Diphyllin and its derivatives have demonstrated V-ATPase inhibition, anti-tumor, anti-virus, anti-biofilm, anti-inflammatory, and anti-oxidant activities. The most studied activities of diphyllin and its derivatives are V-ATPase inhibition, anti-tumor activities, and anti-virus activities. Furthermore, V-ATPase inhibition activity is the mechanism of many bioactivities, including anti-tumor, anti-virus, and anti-inflammatory activities. We also found that the galactosylated modification of diphyllin is a common phenomenon in plants, and therefore, galactosylated modification is applied by researchers in the laboratory to obtain more excellent diphyllin derivatives. This review will provide useful information for the development of diphyllin-based anti-tumor and anti-virus compounds.
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Lignanos , Adenosina Trifosfatasas , Antiinflamatorios/farmacología , Lactonas , Lignanos/farmacología , Lignanos/químicaRESUMEN
OBJECTIVE: To explore the anti-virus effect of AY358935 gene cloned by our research team on vesicular stomatitis virus (VSV), and studytheanti-virus mechanism. METHODS: HEK293 cells were stably transfected by the AY358935 gene recombinant plasmid pcDNA3.1-AY358935 or pcDNA3.1 blank plasmid respectively. Then VSV was added into the cell wells to infect the above cells at the multiplicity of infection (MOI) of 0.001. The virus titers in the liquid supernatant of the above three groups of cells were detected on different time, and the mortality of cells of each group was tested with trypan blue exclusion test at 24 h post VSV infection. Total RNA was extracted from the cells that stably transfected with target gene for the whole genome-wide cDNA microarray analysis. RESULTS: â Virus titer:The virus titer in the liquid supernatant of pcDNA-3.1-AY358935 transfection cells group was obviously lower than those in pcDNA-3.1 transfection cell group and blank control cell group at 12 h post infection. The virus titerin the liquid supernatant of three groups were (7.16±2.33)×105 PFU/mL, (6.25±2.05)×106 PFU/mL and (7.75±2.54)×106 PFU/mL respectively at 18 h post infection. At that time, the virus titerin the liquid supernatant of pcDNA3.1-AY358935 group was nearly 10 times lower than those of other two groups (P < 0.01). â¡Mortality of cells:The cell mortality of pcDNA3.1-AY358935 group, pcDNA3.1 group and blank group were (35.00±6.68)%, (78.33±15.03)% and (83.34±14.98)% respectively at 24 h post infection.The cell mortality of pcDNA3.1-AY358935 group was significantly decreased comparing with other two groups (P < 0.01). â¢Result of genes chip analysis: compared with pcDNA3.1 group, 30 cell genes were up-regulated by more than 3 times in pcDNA3.1-AY358935 group. Among them, the proportion of interferon-activating gene, interferon-effect gene, cytokine and chemokine was 27%, 17%, and 20%, respectively. CONCLUSION: AY358935 gene hasan anti-VSV effect, and its anti-virus mechanism may involve the interferon-associated natural immune response.
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Proteínas Portadoras/genética , Estomatitis Vesicular/inmunología , Animales , Citocinas , Células HEK293 , Humanos , Interferones , Plásmidos , Transfección , VesiculovirusRESUMEN
Diabetic nephropathy (DN) is one of the most important diabetic microangiopathies. The epithelial-to-mesenchymal transition (EMT) plays an important role in DN. The physiological role of microRNA-21 (miR-21) was closely linked to EMT. However, it remained elusive whether tongxinluo (TXL) ameliorated renal structure and function by regulating miR-21-induced EMT in DN. This study aimed to determine the effect of TXL on miR-21-induced renal tubular EMT and to explore the relationship between miR-21 and TGF-ß1/smads signals. Real-time RT-PCR, cell transfection, in situ hybridization (ISH), and laser confocal microscopy were used, respectively. Here, we revealed that TXL dose dependently lowered miR-21 expression in tissue, serum, and cells. Overexpression of miR-21 can enhance α-smooth muscle actin (SMA) expression and decrease E-cadherin expression by upregulating smad3/p-smad3 expression and downregulating smad7 expression. Interestingly, TXL also increased E-cadherin expression and decreased α-SMA expression by regulating miR-21 expression. More importantly, TXL decreased collagen IV, fibronectin, glomerular basement membrane, glomerular area, and the albumin/creatinine ratio, whereas it increased the creatinine clearance ratio. The results demonstrated that TXL ameliorated renal structure and function by regulating miR-21-induced EMT, which was one of the mechanisms to protect against DN, and that miR-21 may be one of the therapeutic targets for TXL in DN.
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Nefropatías Diabéticas/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Transición Epitelial-Mesenquimal/efectos de los fármacos , MicroARNs/metabolismo , Cadherinas/metabolismo , Diferenciación Celular/efectos de los fármacos , Diferenciación Celular/genética , Línea Celular , Nefropatías Diabéticas/genética , Nefropatías Diabéticas/metabolismo , Células Epiteliales/citología , Células Epiteliales/efectos de los fármacos , Transición Epitelial-Mesenquimal/genética , HumanosRESUMEN
Background: The beet armyworm, Spodoptera exigua (Hübner), is an important agricultural pest worldwide that has caused serious economic losses in the main crop-producing areas of China. To effectively monitor and control this pest, it is crucial to investigate its population dynamics and seasonal migration patterns in northern China. Methods: In this study, we monitored the population dynamics of S. exigua using sex pheromone traps in Shenyang, Liaoning Province from 2012 to 2022, combining these data with amigration trajectory simulation approach and synoptic weather analysis. Results: There were significant interannual and seasonal variations in the capture number of S. exigua, and the total number of S. exigua exceeded 2,000 individuals in 2018 and 2020. The highest and lowest numbers of S. exigua were trapped in September and May, accounting for 34.65% ± 6.81% and 0.11% ± 0.04% of the annual totals, respectively. The average occurrence period was 140.9 ± 9.34 days during 2012-2022. In addition, the biomass of S. exigua also increased significantly during these years. The simulated seasonal migration trajectories also revealed varying source regions in different months, primarily originated from Northeast China and East China. These unique insights into the migration patterns of S. exigua will contribute to a deeper understanding of its occurrence in northern China and provide a theoretical basis for regional monitoring, early warning, and the development of effective management strategies for long-range migratory pests.
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Agricultura , Humanos , Animales , Spodoptera , Estaciones del Año , Dinámica Poblacional , China/epidemiologíaRESUMEN
Organic fertilizer substitution has been promoted as a weight loss, efficient, and diversified fertilizer substitution technology in agricultural production. However, there is a lack of comprehensive assessment of the impact of organic fertilizers on N2O and NO emissions from orchards. In this study, N2O and NO emissions from peach orchards were observed annually using static dark box-gas chromatography to compare the effects of chemical fertilizer application alone and partial replacement of chemical fertilizer treatment on NO emissions from peach orchards. The results showed that the partial replacement of chemical fertilizers with organic fertilizers reduced the total N2O and NO emissions from peach orchards by 15.0 % and 9.4 %, respectively. The N2O and NO emission factors were reduced by 21.3 % and 21.1 %. The mineral N content of the soil in the organic fertilizer treatment was lower than that in the chemical fertilizer treatment alone. The organic fertilizer treatment increased the contribution of AOA to nitrification and decreased the contribution of AOB, thus reducing N2O and NO from nitrification. In addition, the results of the dual isotope mixing model[δ18O(N2O/H2O) vs. δ15NSP] indicated that the bacterial denitrification/nitrifying bacterial denitrification (bD/nD) process served as the primary pathway for N2O emissions in peach orchards. Partial substitution with organic fertilizers enhanced soil denitrification, resulting in larger reductions in the amounts of N2O and NO. Therefore, partial substitution of organic fertilizer is a viable measure to mitigate nitrogen oxide emissions from orchards and to achieve green and low-carbon development in agriculture.
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The current strategy of co-delivering copper ions and disulfiram (DSF) to generate cytotoxic CuET faces limitations in achieving rapid and substantial CuET production, specifically in tumor lesions. To overcome this challenge, we introduce a novel burst-release cascade reactor composed of phase change materials (PCMs) encapsulating ultrasmall Cu2-xSe nanoparticles (NPs) and DSF (DSF/Cu2-xSe@PCM). Once triggered by second near-infrared (NIR-II) light irradiation, the reactor swiftly releases Cu2-xSe NPs and DSF, enabling catalytic reactions that lead to the rapid and massive production of Cu2-xSe-ET complexes, thereby achieving in situ chemotherapy. The mechanism of the burst reaction is due to the unique properties of ultrasmall Cu2-xSe NPs, including their small size, multiple defects, and high surface activity. These characteristics allow DSF to be directly reduced and chelated on the surface defect sites of Cu2-xSe, forming Cu2-xSe-ET complexes without the need for copper ion release. Additionally, Cu2-xSe-ET has demonstrated a similar (to CuET) anti-tumor activity through increased autophagy, but with even greater potency due to its unique two-dimensional-like structure. The light-triggered cascade of interlocking reactions, coupled with in situ explosive generation of tumor-suppressive substances mediated by the size and valence of Cu2-xSe, presents a promising approach for the development of innovative nanoplatforms in the field of precise tumor chemotherapy.
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OBJECTIVE: To study the use of Chinese medicine (CM) in cancer patients in southern China. METHODS: A total of 1,950 cancer patients finished questionnaires in four provinces in southern China. The survey included socio-demographic and clinical characteristics of participants, dosage forms, efficacy, and side effects. RESULTS: The study results showed that cancer patients with higher education (>12 years) were more likely to accept the treatment of Chinese herbs. There were 54.61% (1,065 cases) of patients chose Chinese herbs for the initial treatment and 14.46% (282 cases) chose Chinese herbs as monotherapy. Most patients (54.51%, 1,063 cases) continuously used CM for more than 6 months, and a few of them (212 cases) used CM for up to 3 years. All kinds of dosage forms of CM had been used, including CM decoction, CM patent prescription and CM injection. Concerning the efficacy in the view of patients, 40.31% (786 cases) believed that it would be effective to take Chinese herbs before they starting the anti-cancer treatment, and the percentage increased to 81.08% after 1-month CM treatment. The effect of Chinese herbs was mainly demonstrated by symptom relief and improvement of quality of life, and 8.31% (162 cases) of patients experienced control of tumor growth and decreased tumor markers. Furthermore, only 14.31% (279 cases) participants reported that they experienced side effects during CM treatment. CONCLUSION: This large scale investigation reflects the current situation of domestic CM usage objectively and comprehensively, which might provide new ways for cancer treatment.
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Medicamentos Herbarios Chinos , Neoplasias , China , Medicamentos Herbarios Chinos/efectos adversos , Humanos , Medicina Tradicional China , Neoplasias/tratamiento farmacológico , Calidad de Vida , Encuestas y CuestionariosRESUMEN
BACKGROUND: TARDBP mutations have been reported in patients with amyotrophic lateral sclerosis (ALS) in different populations except Chinese. The present aim is to investigate the association between TARDBP mutations and Chinese patients with ALS. METHODS: 71 SALS patients and 5 FALS families with non-SOD1 mutations were screened for TARDBP mutations via direct sequencing. RESULTS: A novel heterozygous variation, Ser292Asn (875G>A), was identified in the proband and 4 asymptomatic relatives including the children of the dead patient from a FALS family. Thus the dead patient, the proband's brother, was speculated to carry Ser292Asn though his sample was unavailable to the detection. This variation was not found in 200 unrelated control subjects. A homology search of the TDP-43 protein in different species demonstrated that it was highly conserved. Also, it was predicted to be deleterious to protein function with SIFT-calculated probabilities of 0.00. Therefore, Ser292Asn is predicted to be a pathogenic mutation. In addition, we have found two silent mutations (Gly40Gly and Ala366Ala) and one novel polymorphism (239-18t>c). CONCLUSIONS: The present data have extended the spectrum of TARDBP mutations and polymorphisms, and supported the pathological role of TDP-43 in Chinese ALS patients.
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Esclerosis Amiotrófica Lateral/genética , Pueblo Asiatico/genética , Proteínas de Unión al ADN/genética , Mutación , Adulto , Anciano , Secuencia de Aminoácidos , Sustitución de Aminoácidos , Esclerosis Amiotrófica Lateral/etnología , China , Cromosomas Humanos Par 1 , Humanos , Persona de Mediana Edad , Datos de Secuencia Molecular , Linaje , Polimorfismo de Nucleótido Simple , Alineación de Secuencia , Análisis de Secuencia de ADNRESUMEN
Liver-enriched gene 1 (Leg1) is a newly identified gene with little available functional information. To evolutionarily and molecularly characterize Leg1 genes, a phylogenetic study was first conducted, which indicated that Leg1 is a conserved gene that exists from bacteria to mammals. During the evolution of mammals, Leg1s underwent tandem duplications, which gave rise to Leg1a, Leg1b, and Leg1c clades. Analysis of the pig genome showed the presence of all three paralogs of pig Leg1 genes (pLeg1s), whereas only Leg1a could be found in the human (hLeg1a) or mouse (mLeg1a) genomes. Purifying force acts on the evolution of Leg1 genes, likely subjecting them to functional constraint. Molecularly, pLeg1a and its coded protein, pig LEG1a (pLEG1a), displayed high similarities to its human and mouse homologs in terms of gene organization, expression patterns, and structures. Hence, pLeg1a, hLeg1a, and mLeg1a might preserve similar functions. Additionally, expression analysis of the three Leg1as suggested that eutherian Leg1as might have different functions from those of zebrafish and platypus due to subfunctionalization. Therefore, pLeg1a might provide essential information about eutherian Leg1a. Moreover, a preliminary functional study using RNA-seq suggested that pLeg1a is involved in the lipid homeostasis. In conclusion, our study provides some basic information on the aspects of evolution and molecular function, which could be applied for further validation of Leg1 using pig models.
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Evolución Molecular , Proteínas/genética , Animales , Evolución Biológica , Clonación Molecular , Genoma , Genómica/métodos , Humanos , Ratones , Filogenia , Proteínas/química , Análisis de Secuencia de ARN , Relación Estructura-Actividad , Proteínas de Pez Cebra/química , Proteínas de Pez Cebra/genéticaRESUMEN
While the studies on the material interaction with mesenchymal stem cells (MSCs) have been mainly focused on the ability of materials to provide environment to regulate cell viability, proliferation or differentiation, the therapeutic effects of MSC-material constructs may result from the secretion of immunomodulatory and angiogenic cytokines from MSCs. Here, electrospun scaffolds composed of fibers in random, aligned and mesh-like patterns were fabricated, and the paracrine behavior of adipose-derived MSCs (Ad-MSCs) on the scaffolds were investigated in comparison to the cell culture via conventional microplates. It was found that the Ad-MSCs on the electrospun fibers produced significantly higher levels of anti-inflammatory and pro-angiogenic cytokines compared to those cultured on microplates. The enhanced modulatory effects of the secreted products of Ad-MSCs on fibrous electrospun scaffolds were also proven in the cultures of endothelial cells and the LPS-stimulated macrophages, with three types of scaffolds showing distinct influences on the paracrine function of Ad-MSCs. In a skin excisional wound-healing model in rat, the conditioned medium collected from the MSC-scaffold system accelerated the wound closure, promoted the macrophage recruitment and enhanced the polarization of macrophages toward the pro-healing phenotype in the wound bed. Our study demonstrates that the fibrous topography of scaffolds is a key material property that modulates the paracrine function of cells. The discovery elucidates a new aspect of material functions, laying the foundation for developing scaffold materials to promote tissue regeneration/repair through guiding the paracrine signaling network.
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Células Madre Mesenquimatosas/citología , Nanofibras/química , Comunicación Paracrina , Andamios del Tejido/química , Tejido Adiposo/citología , Animales , Línea Celular , Células Cultivadas , Regulación de la Expresión Génica , Células Endoteliales de la Vena Umbilical Humana , Humanos , Células Madre Mesenquimatosas/metabolismo , Nanofibras/ultraestructura , Neovascularización Fisiológica , Ratas , Propiedades de Superficie , Cicatrización de HeridasRESUMEN
Doxorubicin (DOX) has been widely used to treat cancers as a firstline antitumor drug. However, it causes severe, irreversible, dosedependent cardiotoxicity. To evaluate the protective effects of naringin (NRG) on cardiotoxicity, the authors investigated the molecular mechanism of the p38MAPK signaling pathway. H9c2 cells were treated for 24 h by using 5 µmol/l DOX without or with being pretreated by 1 µM NRG for 150 min or by 3 µM SB203580 for 60 min. Cell viability was detected by cell counting kit8 assay. Intracellular reactive oxygen species (ROS) levels were detected based on the oxidative conversion of 2',7'dichlorfluoresceindiacetate (cellpermeable) to dichlorofluorescein (fluorescent). The expression of p38MAPK was determined by western blotting. The expression level of pp38MAPK in H9c2 cells, which was significantly increased by exposure to 5 µM DOX for 60 min (P<0.01), was significantly decreased by pretreatment with 1 µM NRG for 150 min beforehand (P<0.01). The viability of H9c2 cells pretreated for 150 min with 1 µM NRG was significantly enhanced compared with that using DOX directly (P<0.01). Intracellular ROS levels were significantly reduced by being pretreated with 1 µM NRG for 150 min or with 3 µM SB203580 for 60 min before the cells were exposed to 5 µM DOX. Collectively, NRG protected H9c2 cells against the cardiotoxicity induced by DOX through suppressing the expression and activity of the p38MAPK pathway. The findings provided valuable evidence for the possible use of NRG to relieve DOXinduced cardiotoxicity.
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Cardiotoxicidad/tratamiento farmacológico , Doxorrubicina/efectos adversos , Flavanonas/administración & dosificación , Proteínas Quinasas p38 Activadas por Mitógenos/genética , Animales , Apoptosis/efectos de los fármacos , Cardiotoxicidad/etiología , Cardiotoxicidad/genética , Cardiotoxicidad/patología , Supervivencia Celular/efectos de los fármacos , Doxorrubicina/administración & dosificación , Humanos , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/patología , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Ratas , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Biodegradable plastics and hydrogels possess distinct mechanical/biocompatibility properties that are indispensible in device design. It is desirable to combine their advantages by creating hybrid materials/structures. Here, a new method based on a reversible addition-fragmentation chain transfer (RAFT) reaction was demonstrated by direct polymerization of polyethylene glycol (PEG) hydrogel network on polycaprolactone (PCL) electrospun fibers. The resulting hybrid fibrous matrices exhibited unique material characteristics-including high-speed water absorption without visible matrix deformation and plastic bulk properties with low surface elasticity-that were otherwise nonachievable in plastics or hydrogels alone. The mechanically strong, water-absorbing fibrous composite materials can potentially find important applications in biomedical devices.
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BACKGROUND: Midgastric transverse band (MTB) was first observed over 100 years ago, after that many researchers worked on the subject postulated its physiologic role and the role in gastrointestinal diseases, but its function remains unclear. With progress of imaging methods, the nature of MTB is unveiling. In this study we investigated the effect of MTB on the gastric emptying delay in functional dyspepsia (FD) and explored the mechanism. METHODS: A total of 60 patients with FD and 65 age- and sex-matched healthy people who served as controls were studied. With (99m)Tc-DTPA labeled semi-solid fat-parched flour served as test meal, gastric emptying was examined in all subjects by using single photon emission computed tomography. Test meal was designated as general (60 g fat-parched flour) or large (80 g fat-parched flour) meal. Stomach was divided into proximal and distal parts by MTB. Half gastric emptying time, areas of different gastric parts, intragastric food distribution and MTB width were tested with in given times. RESULTS: Patients with FD showed a delayed gastric emptying and increased intragastric residue. Global and regional gastric emptying velocity was decreased. The areas of distal stomach and MTB were significantly greater in the FD patients than in the controls. Throughout the whole test period a distal stomach-dominated food distribution was shown. Those who took a large meal had longer half gastric emptying time and greater MTB area than those who took a general meal. CONCLUSIONS: Gastric emptying delay is related to enlarged MTB area. Some dyspeptic symptoms may be induced by abnormal distribution and increased retention of food in distal stomach. MTB, being like atria-ventricular valve that controls blood flow in heart, regulates transport, distribution, and emptying of food in the stomach.
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Dispepsia/fisiopatología , Vaciamiento Gástrico/fisiología , Contracción Muscular , Estómago/fisiología , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de TiempoRESUMEN
OBJECTIVE: To study the expressions of CD55 and CD59 in patients with hyperlipidemia and the effects of atorvastatin on it, and to identify the possible influential factors. METHODS: We selected 67 patients with hyperlipidemia, and 24 healthy people matched in terms of age, sex and body weight as control. The expressions of CD55 and CD59 on white blood cells were detected by flow cytometry, and their relationships to blood lipids, complement activation indexes (C(5a), sC(5b-9)), inflammatory factors (high sensitivity C-reactive protein (hsCRP), TNF-alpha, IL-6 were analyzed. 24 patients with hyperlipidemia were treated with atorvastatin for 8-12 weeks and the expressions of CD55 and CD59 were measured before and after atorvastatin therapy. RESULTS: The mean fluorescence intensity (MFI) of CD55 lymphocytes and monocytes were decreased in patients with hyperlipidemia compared with control (2.07 +/- 0.28 vs 2.29 +/- 0.44 and 3.45 +/- 1.02 vs 4.33 +/- 2.32, P < 0.01 and P < 0.05, respectively). CD55 positive lymphocyte MFI was negatively correlated with waist circumference, waist-hip ratio, hsCRP and C(5a). C(5a) was negatively correlated with the MFIs of CD55 positive lymphocytes, monocytes, granulocytes, and positively with TG and diastolic blood pressure. After atorvastatin therapy, the MFIs of CD59 positive lymphocytes, monocytes and granulocytes increased (4.34 +/- 1.16 vs 3.69 +/- 0.76, 4.52 +/- 1.36 vs 3.91 +/- 0.89, 5.67 +/- 1.72 vs 4.56 +/- 1.03, P < 0.05, < 0.05 and < 0.01 respectively), which were not correlated with changes of blood lipids. CONCLUSIONS: The expression of CD55 is down-regulated in hyperlipidemia, which might be influenced by obesity, abdominal distribution of adipose tissue and inflammatory status of hyperlipidemia, but not by blood lipids. The expression of CD55 is related with complement activation; The expression of CD59 is up-regulated after atorvastatin treatment independently of blood lipids.
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Antígenos CD55/metabolismo , Antígenos CD59/metabolismo , Ácidos Heptanoicos/uso terapéutico , Hiperlipidemias/metabolismo , Hipolipemiantes/uso terapéutico , Pirroles/uso terapéutico , Anciano , Atorvastatina , Estudios de Casos y Controles , Activación de Complemento , Regulación de la Expresión Génica , Humanos , Hiperlipidemias/tratamiento farmacológico , Hiperlipidemias/inmunología , Masculino , Persona de Mediana EdadRESUMEN
Epithelial-to-mesenchymal transition (EMT) plays an important role in renal interstitial fibrosis (RIF) with diabetic nephropathy (DN). Smad7 (a inhibitory smad), a downstream signaling molecules of TGF-ß1, represses the EMT. The physiological function of miR-21 is closely linked to EMT and RIF. However, it remained unclear whether miR-21 over-expression affected TGF-ß1-induced EMT by regulating smad7 in DN. In this study, real-time RT-PCR, cell transfection, luciferase reporter gene assays, western blot and confocal microscope were used, respectively. Here, we found that miR-21 expression was upregulated by TGF-ß1 in time- and concentration -dependent manner. Moreover, miR-21 over-expression enhanced TGF-ß1-induced EMT(upregulation of a-SMA and downregulation of E-cadherin) by directly down-regulating smad7/p-smad7 and indirectly up-regulating smad3/p-smad3, accompanied by the decrease of Ccr and the increase of col-IV, FN, the content of collagen fibers, RTBM, RTIAW and ACR. Meantime, the siRNA experiment showed that smad7 can directly regulate a-SMA and E-cadherin expression. More importantly, miR-21 inhibitor can not only inhibit EMT and fibrosis but also ameliorate renal structure and function. In conclusion, our results demonstrated that miR-21 overexpression can contribute to TGF-ß1-induced EMT by inhibiting target smad7, and that targeting miR-21 may be a better alternative to directly suppress TGF-ß1-mediated fibrosis in DN.
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Nefropatías Diabéticas/patología , Transición Epitelial-Mesenquimal/efectos de los fármacos , Riñón/patología , MicroARNs/metabolismo , Proteína smad7/metabolismo , Factor de Crecimiento Transformador beta1/farmacología , Actinas/metabolismo , Animales , Secuencia de Bases , Biomarcadores/metabolismo , Cadherinas/metabolismo , Línea Celular , Nefropatías Diabéticas/genética , Regulación hacia Abajo/efectos de los fármacos , Transición Epitelial-Mesenquimal/genética , Humanos , Riñón/efectos de los fármacos , Riñón/ultraestructura , Masculino , Ratones Endogámicos C57BL , MicroARNs/genética , Datos de Secuencia Molecular , Fosforilación/efectos de los fármacos , Proteína smad3/genética , Proteína smad3/metabolismo , Proteína smad7/genética , Regulación hacia Arriba/efectos de los fármacosRESUMEN
Taking a rice-wheat rotation system in the suburb of Nanjing, Jiangsu Province of East China as test object, this paper studied the fluxes of CH4 and N2O and their annual dynamics under different farming managements in 2010-2011, and the field observation data were applied to validate the process-based model, denitrification-decomposition (DNDC) model, aimed to approach the applicability of the model to this rotation system, and to use this model to simulate the effects of different environmental factors and farming managements on the global warming potentials (GWPs) of CH4 and N2O. The results showed that except in the treatment control and during wheat growth season, the simulated cumulative emissions of CH4 and N2O from the rotation system in all treatments were basically in coincide with the observed data, the relative deviations being from 7. 1% to 26.3%, and thus, the DNDC model could be applied to simulate the GWPs of cumulative emissions of CH4 and N2O as affected by various environmental factors or management practices. The sensitivity test showed that the GWPs of CH4 and N2O varied significantly with the changes of environmental factors such as the mean annual air temperature, soil bulk density, soil organic carbon, soil texture, and soil pH. Farming managements such as N fertilization, straw returning, and duration of mid-season drainage also had significant effects on the GWPs of CH4 and NO20. Therefore, the above-mentioned environmental factors and farming managements should be taken into account to estimate the greenhouse gases emission from the rice-wheat cropping system on site-specific or regional scale.
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Agricultura/métodos , Calentamiento Global , Metano/análisis , Óxido Nitroso/análisis , Oryza/crecimiento & desarrollo , Triticum/crecimiento & desarrollo , China , Monitoreo del Ambiente , Modelos TeóricosRESUMEN
Diabetic peripheral neuropathy (DPN) is a common microvascular complication of diabetes associated with high disability rate and low quality of life. Tang-Luo-Ning (TLN) is an effective traditional Chinese medicine for the treatment of DPN. To illustrate the underlying neural protection mechanisms of TLN, the effect of TLN on electrophysiology and sciatic nerve morphology was investigated in a model of streptozotocin-induced DPN, as well as the underlying mechanism. Sciatic motor nerve conduction velocity and digital sensory nerve conduction velocity were reduced in DPN and were significantly improved by TLN or α -lipoic acid at 10 and 20 weeks after streptozotocin injection. It was demonstrated that TLN intervention for 20 weeks significantly alleviated pathological injury as well as increased the phosphorylation of ErbB2, Erk, Bad (Ser112), and the mRNA expression of neuregulin 1 (Nrg1), GRB2-associated binding protein 1 (Gab1), and mammalian target of rapamycin (Mtor) in injured sciatic nerve. These novel therapeutic properties of TLN to promote Schwann cell survival may offer a promising alternative medicine for the patients to delay the progression of DPN. The underlying mechanism may be that TLN exerts neural protection effect after sciatic nerve injury through Nrg1/ErbB2âErk/Bad Schwann cell survival signaling pathway.
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To investigate the dynamic distribution patterns of nitrous oxide (N2O) in the soil profiles in paddy fields with different rice-upland crop rotation systems, a special soil gas collection device was adopted to monitor the dynamics of N2O at the soil depths 7, 15, 30, and 50 cm in the paddy fields under both flooding and drainage conditions. Two rotation systems were installed, i.e., wheat-single rice and oilseed rape-double rice, each with or without nitrogen (N) application. Comparing with the control, N application promoted the N2O production in the soil profiles significantly (P < 0.01), and there existed significant correlations in the N2O concentration among the four soil depths during the whole observation period (P < 0.01). In the growth seasons of winter wheat and oilseed rape under drainage condition and with or without N application, the N2O concentrations at the soil depths 30 cm and 50 cm were significantly higher than those at the soil depths 7 cm and 15 cm; whereas in the early rice growth season under flooding condition and without N application, the N2O concentrations at the soil depth 7 cm and 15 cm were significantly higher than those at the soil depths 30 cm and 50 cm (P < 0.05). No significant differences were observed in the N2O concentrations at the test soil depths among the other rice cropping treatments. The soil N2O concentrations in the treatments without N application peaked in the transitional period from the upland crops cropping to rice planting, while those in the treatments with N application peaked right after the second topdressing N of upland crops. Relatively high soil N2O concentrations were observed at the transitional period from the upland crops cropping to rice planting.
Asunto(s)
Agricultura/métodos , Ecosistema , Óxido Nitroso/análisis , Oryza/crecimiento & desarrollo , Suelo/análisis , Brassica/crecimiento & desarrollo , Monitoreo del Ambiente/métodos , Triticum/crecimiento & desarrolloRESUMEN
OBJECTIVE: To study the epilepsy patients and their family members on their knowledge of the disease. METHODS: A 34-point questionnaire with 34 questions related to epilepsy knowledge was used for the survey on 170 pairs of epilepsy patients and their family members in Huashan hospital. Characters of the disease on the subjects were recorded. RESULTS: The mean scores of the epilepsy knowledge of the patients and their family members were 16.5 +/- 8.2 and 16.1 +/- 8.5, respectively. The scores were quite low with no statistical difference between patients and their family members. The rate of correct answer in the urban subjects was obviously higher than those subjects living in the rural areas. All the subjects lacked the knowledge on the "cause of disease" when comparing with items as "diagnosis" and "treatment". Multivariate analysis showed that rural residents (P = 0.0001, OR = 52.963) and low education level (P = 0.0294, OR = 2.266) related to low epilepsy knowledge score among epilepsy patients. However, for family members, the factor related to low score was only living in the rural area (P = 0.0001, OR = 37.229). CONCLUSION: Education on the epilepsy knowledge should be strengthened, especially in the rural areas.