RESUMEN
In the kidney, vasoactive peptide hormones angiotensin II (Ang II), via AT1a receptors, and atrial natriuretic peptide (ANP), via NPRA receptors, reportedly play counteracting roles to regulate proximal tubule Na+ reabsorption and maintain blood pressure homeostasis. However, how AT1a and NPRA receptors interact in the proximal tubules and whether deletion of AT1 (AT1a) receptors selectively in the proximal tubules alters the hypotensive and natriuretic effects of ANP) have not been studied previously. The present study used a novel mouse model with proximal tubule-specific knockout of AT1a receptors to test the hypothesis that deletion of AT1a receptors selectively in the proximal tubules augments the hypotensive and natriuretic responses to ANP. Basal blood pressure was about 16 ± 3 mmHg lower, fractional proximal tubule Na+ reabsorption was significantly lower, whereas 24 h urinary Na+ excretion was significantly higher in PT-Agtr1a-/- than in wild-type mice (P<0.01). Infusion of ANP for 2 weeks (0.5 mg/kg/day, i.p.) further significantly decreased blood pressure and increased the natriuretic response in PT-Agtr1a-/- mice by inhibiting proximal tubule Na+ reabsorption (P<0.01). These augmented hypotensive and natriuretic responses to ANP in PT-Agtr1a-/- mice were associated with increased plasma and kidney cGMP levels (P<0.01), kidney cortical NPRA and NPRC mRNA expression (P<0.01), total and phosphorylated endothelial nitric oxide synthase (eNOS) (P<0.01), and urinary nitric oxide (NO) excretion (P<0.01). Taken together, the results of the present study support important physiological roles of Ang II/AT1a and ANP/NPRA signaling pathways in the proximal tubules to regulate proximal tubule reabsorption and maintain blood pressure homeostasis.
RESUMEN
We systematically investigated the stable configurations and catalytic activity in the Oxygen Reduction Reaction (ORR) of graphene co-doped with boron and nitrogen (B-N) using first-principles methods. Compared to single B/N doping, co-doping with BN is energetically favored. We found that intermediate species of ORR process adsorb on boron atoms, which act as catalytic sites. The presence of neighboring nitrogen atoms around boron plays a crucial role in modulating the catalytic activity of boron. For the same adsorption configuration, the adsorption energy of the adsorbate increases with the number of neighboring nitrogen atoms around boron and generally correlates positively with the number of electrons gained by the adsorbate. Regarding the catalytic activity of ORR, excessively strong adsorption of adsorbates impedes their hydrogenation. The best substrates for ORR catalytic activity are B-N-graphene and N-B2-graphene, with the rate-determining step being the hydrogenation of *OO and overpotentials of 0.49â V and 0.54â V, respectively.
RESUMEN
An important step during the workflow of complete arch fixed implant-supported prostheses is the fabrication of an acrylic resin prototype prosthesis so that the patient can visualize the definitive treatment outcome or to be used as an interim prosthesis. The prototype prosthesis is typically designed digitally as a single file and is produced by milling from a solid block of white-colored prepolymerized acrylic resin. A common challenge in fabricating a resin-based prototype prosthesis is reproducing the natural appearance of the gingival architecture in gingiva-colored material. Current methods, including multicolored resin blocks, gingiva-colored stain, and layering with gingiva-colored composite resin, can be costly, time-consuming, and labor-intensive. This article describes a straightforward chairside technique that allows clinicians to fabricate an acrylic resin prototype prosthesis with appropriate gingival esthetics.
Asunto(s)
Implantes Dentales , Encía , Humanos , Resinas Acrílicas , Prótesis Dental de Soporte Implantado/métodos , Estética DentalRESUMEN
PURPOSE: To determine the survival rates of implant-supported monolithic zirconia crowns and fixed partial dentures (FPD). MATERIAL AND METHODS: An electronic search for articles in the English language literature published from January 1, 2001 to September 17, 2021 was performed using PubMed, Scopus, and CENTRAL search engines. After applying predetermined inclusion and exclusion criteria, the definitive list of selected articles was used for calculating the interval survival rate (ISR) and cumulative survival rate (CSR). Restoration failure in this study was defined as the fracture or compromise of any part of the ceramic restoration that required the removal or remake of the implant-supported restoration. RESULTS: The electronic search resulted in 457 titles. The systematic application of inclusion and exclusion criteria resulted in 14 clinical studies that addressed the clinical outcomes of implant-supported monolithic zirconia crowns and fixed partial dentures. Of these, 3 were randomized controlled trials, 5 were prospective studies, and 6 were retrospective studies. Follow-up periods ranged from 1 to 5 years. Of the 644 implant-supported monolithic zirconia restorations computed in this systematic review, there was only 1 reported failure of the monolithic zirconia restorative material over a follow-up period of up to 5 years, for a cumulative survival rate of 99.84%. At the maximum follow-up interval of 5 years, the cumulative survival rate for monolithic zirconia single crowns was 100% and the cumulative survival rate for monolithic zirconia fixed partial dentures was 99.60%. CONCLUSIONS: Implant-supported monolithic zirconia single crowns and fixed partial dentures have excellent short-term (<5 years) survival rates but the evidence for medium-term survival (>5 years) and beyond is lacking.
Asunto(s)
Implantes Dentales , Diseño de Prótesis Dental , Estudios Retrospectivos , Estudios Prospectivos , Fracaso de la Restauración Dental , Coronas , Circonio , Dentadura Parcial Fija , Prótesis Dental de Soporte ImplantadoRESUMEN
Electrical stimulation of the right median nerve can aid coma arousal after traumatic brain injury (TBI). This study aimed to confirm the efficacy further and explore possible mechanisms of right median nerve electrical stimulation (RMNS). Five comatose patients after severe TBI from May to September 2020 in the Tianjin Medical University General Hospital received RMNS for 2 weeks besides standard management. After the 2-week treatment, the mean Glasgow Coma Scale (GCS) and neurophysiological examination were used. We then investigated the alterations in microRNA (miRNA) expression in cerebrospinal fluid (CSF) by high-throughput whole transcriptome sequencing, analyzed the data by Gene Ontology (GO) and pathway analysis, and constructed the miRNA-target gene network. Patient awareness and brain function showed a more rapid increase after treatment. We also found 38 differently expressed miRNAs, 34 of which were upregulated and 4 downregulated. GO analysis showed a relation of these differentially expressed miRNAs with neuronal growth, repair, and neural signal transmission. The most highly correlated pathways were primarily associated with the tumor necrosis factor (TNF) signaling pathway and dopaminergic synapse. The application of RMNS effectively promoted early awakening in comatose patients with severe TBI. Moreover, differentially expressed miRNAs might reduce neuronal apoptosis and increase dopamine levels by regulating target gene expression, thus participating in the specific biological process after arousal therapy. Our study provided novel targets for further research on the molecular mechanisms of RMNS arousal treatment and a new way to treat neurotraumatic diseases.
Asunto(s)
Lesiones Traumáticas del Encéfalo , MicroARNs , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/genética , Lesiones Traumáticas del Encéfalo/metabolismo , Coma/etiología , Coma/terapia , Escala de Coma de Glasgow , Humanos , Nervio MedianoRESUMEN
The roles of angiotensin II (Ang II) AT1 (AT1a) receptors and its downstream target Na+/H+ exchanger 3 (NHE3) in the proximal tubules in the development of two-kidney, 1-clip (2K1C) Goldblatt hypertension have not been investigated previously. The present study tested the hypothesis that deletion of the AT1a receptor or NHE3 selectively in the proximal tubules of the kidney attenuates the development of 2K1C hypertension using novel mouse models with proximal tubule-specific deletion of AT1a receptors or NHE3. 2K1C Goldblatt hypertension was induced by placing a silver clip (0.12 mm) on the left renal artery for 4 weeks in adult male wild-type (WT), global Agtr1a−/−, proximal tubule (PT)-specific PT-Agtr1a−/− or PT-Nhe3−/− mice, respectively. As expected, telemetry blood pressure increased in a time-dependent manner in WT mice, reaching a maximal response by Week 3 (p < 0.01). 2K1C hypertension in WT mice was associated with increases in renin expression in the clipped kidney and decreases in the nonclipped kidney (p < 0.05). Plasma and kidney Ang II were significantly increased in WT mice with 2K1C hypertension (p < 0.05). Tubulointerstitial fibrotic responses were significantly increased in the clipped kidney (p < 0.01). Whole-body deletion of AT1a receptors completely blocked the development of 2K1C hypertension in Agtr1a−/− mice (p < 0.01 vs. WT). Likewise, proximal tubule-specific deletion of Agtr1a in PT-Agtr1a−/− mice or NHE3 in PT-Nhe3−/− mice also blocked the development of 2K1C hypertension (p < 0.01 vs. WT). Taken together, the present study provides new evidence for a critical role of proximal tubule Ang II/AT1 (AT1a)/NHE3 axis in the development of 2K1C Goldblatt hypertension.
Asunto(s)
Hipertensión Renovascular , Hipertensión , Receptor de Angiotensina Tipo 1 , Intercambiador 3 de Sodio-Hidrógeno , Animales , Masculino , Ratones , Angiotensina II/metabolismo , Presión Sanguínea , Hipertensión/metabolismo , Hipertensión Renovascular/genética , Riñón/metabolismo , Túbulos Renales Proximales/metabolismo , Receptor de Angiotensina Tipo 1/genética , Receptor de Angiotensina Tipo 1/metabolismo , Intercambiador 3 de Sodio-Hidrógeno/genética , Intercambiador 3 de Sodio-Hidrógeno/metabolismo , Eliminación de Gen , Ratones NoqueadosRESUMEN
PURPOSE OF REVIEW: The sodium (Na+) and hydrogen (H+) exchanger 3 (NHE3), known as solute carrier family 9 member 3 (SLC9A3), mediates active transcellular Na+ and bicarbonate reabsorption in the small intestine of the gut and proximal tubules of the kidney. The purpose of this article is to review and discuss recent findings on the critical roles of intestinal and proximal tubule NHE3 in maintaining basal blood pressure (BP) homeostasis and their potential therapeutic implications in the development of angiotensin II (Ang II)-dependent hypertension. RECENT FINDINGS: Recently, our and other laboratories have generated or used novel genetically modified mouse models with whole-body, kidney-specific, or proximal tubule-specific deletion of NHE3 to determine the critical roles and underlying mechanisms of NHE3 in maintaining basal BP homeostasis and the development of Ang II-induced hypertension at the whole-body, kidney, or proximal tubule levels. The new findings demonstrate that NHE3 contributes to about 10 to 15 mmHg to basal blood pressure levels, and that deletion of NHE3 at the whole-kidney or proximal tubule level, or pharmacological inhibition of NHE3 at the kidney level with an orally absorbable NHE3 inhibitor AVE-0657, attenuates ~ 50% of Ang II-induced hypertension in mice. The results support the proof-of-concept hypothesis that NHE3 plays critical roles in physiologically maintaining normal BP and in the development of Ang II-dependent hypertension. Our results also strongly suggest that NHE3 in the proximal tubules of the kidney may be therapeutically targeted to treat poorly controlled hypertension in humans.
Asunto(s)
Hipertensión , Angiotensina II/metabolismo , Animales , Humanos , Hipertensión/tratamiento farmacológico , Túbulos Renales Proximales , Ratones , Intercambiador 3 de Sodio-Hidrógeno , Intercambiadores de Sodio-HidrógenoRESUMEN
Magnesium is a light metal, with a density two-thirds that of aluminium, is abundant on Earth and is biocompatible; it thus has the potential to improve energy efficiency and system performance in aerospace, automobile, defence, mobile electronics and biomedical applications. However, conventional synthesis and processing methods (alloying and thermomechanical processing) have reached certain limits in further improving the properties of magnesium and other metals. Ceramic particles have been introduced into metal matrices to improve the strength of the metals, but unfortunately, ceramic microparticles severely degrade the plasticity and machinability of metals, and nanoparticles, although they have the potential to improve strength while maintaining or even improving the plasticity of metals, are difficult to disperse uniformly in metal matrices. Here we show that a dense uniform dispersion of silicon carbide nanoparticles (14 per cent by volume) in magnesium can be achieved through a nanoparticle self-stabilization mechanism in molten metal. An enhancement of strength, stiffness, plasticity and high-temperature stability is simultaneously achieved, delivering a higher specific yield strength and higher specific modulus than almost all structural metals.
RESUMEN
A versatile solid Poly-methyl-methacrylate (PMMA) composite containing porphyrin-covalently functionalized multi-walled carbon nanotubes (MWNTs-TPP) was prepared through free radical polymerization without additional dispersion stabilizer. Using nanosecond, femtosecond pulse Z-scan and degenerate femtosecond pump-probe techniques, we studied the optical limiting effect, ultrafast saturable absorption and transient differential transmission of the composite. Results show that the solid composite exhibits weaker optical limiting effects than that of the suspension at 532 nm under nanosecond pulse, due to the absence of nonlinear scattering mechanism. The composite also shows ultrafast saturable absorption with a relaxation time about 190 fs at 800 nm under femtosecond pulse due to band-filling effect, comparably to the suspension. The versatile solid composite can be the candidate for uses in applications of ultrafast optical switching and mode-locking element or optical limiter for nanosecond pulse.
RESUMEN
The nonlinear refraction (NLR) properties of graphene oxide (GO) in N, N-Dimethylformamide (DMF) was studied in nanosecond, picosecond and femtosecond time regimes by Z-scan technique. Results show that the dispersion of GO in DMF exhibits negative NLR properties in nanosecond time regime, which is mainly attributed to transient thermal effect in the dispersion. The dispersion also exhibits negative NLR in picosecond and femtosecond time regimes, which are arising from sp(2)- hybridized carbon domains and sp(3)- hybridized matrix in GO sheets. To illustrate the relations between NLR and nonlinear absorption (NLA), NLA properties of the dispersion were also studied in nanosecond, picosecond and femtosecond time regimes.
Asunto(s)
Grafito/química , Óxidos/química , Refractometría/métodos , Absorción , Grafito/efectos de la radiación , Luz , Ensayo de Materiales , Dinámicas no Lineales , Óxidos/efectos de la radiación , Dispersión de RadiaciónRESUMEN
The cement industry faces great pressure from the targets of carbon peak and carbon neutrality. CO2capture, geological utilization, and storage(CCUS) technology is crucial for CO2 mitigation in large-scale fossil-based industries. An integrated techno-economic assessment model of CCUS was improved here to assess the potential of CCUS retrofits in the cement industry in China, and the cost curve or supply curve of CCUS in the cement industry was obtained. The model set up ten scenarios from four aspects:source-sink matching distance, capture rate, CCUS technology, and technical level. The cement enterprise screening, site screening, techno-economic evaluation, and source-sink matching of CCUS were completed to answer some key problems in realizing low-carbon development via CCUS, such as enterprise inventory, storage site, emission reduction scale, and cost range. Under the scenario of 250 km matching distance, 85% net capture rate, CO2-enhanced water recovery technology, and current technical level, 44% of cement enterprises reduced carbon emission via CCUS, the cumulative capacity reached 625 million tons per year, and the levelized cost was 290-1838 yuan·t-1. The projects with a levelized cost of fewer than 600 yuan·t-1 accounted for 77% and could reduce CO2 emission by 564 million tons annually. The projects whose levelized cost was less than 400 yuan·t-1 could reduce CO2 by 199 million tons per year. When the coupling of CO2-enhanced oil recovery and CO2-enhanced water recovery technology was considered, the levelized cost was 27% lower. When the cement capacity was less than 530 million tons per year, the additional cost of cement production was 95-300 yuan·t-1. Under technological progress to 2030, the levelized cost will be reduced by 9%-15%. The regions with early demonstration advantages of full-chain CO2-enhanced water recovery technology were Xinjiang, Inner Mongolia, Ningxia, Henan, and Hebei. Additionally, the areas suitable for cement CCUS cluster included Ordos Basin, Junggar Basin, Bohai Bay Basin, and Songliao Basin. It is technically feasible for the cement industry to deploy full-chain CCUS projects, and low-cost projects have an early demonstration opportunity. These results can provide a quantitative reference for the low-carbon development of the cement industry and the commercial deployment of CCUS in cement production.
RESUMEN
Cardiovascular disease is a pathology that exhibits well-researched biological sex differences, making it possible for physicians to tailor preventative and therapeutic approaches for various diseases. Hypertension, which is defined as blood pressure greater than 130/80â mmHg, is the primary risk factor for developing coronary artery disease, stroke, and renal failure. Approximately 48% of American men and 43% of American women suffer from hypertension. Epidemiological data suggests that during reproductive years, women have much lower rates of hypertension than men. However, this protective effect disappears after the onset of menopause. Treatment-resistant hypertension affects approximately 10.3 million US adults and is unable to be controlled even after implementing ≥3 antihypertensives with complementary mechanisms. This indicates that other mechanisms responsible for modulating blood pressure are still unclear. Understanding the differences in genetic and hormonal mechanisms that lead to hypertension would allow for sex-specific treatment and an opportunity to improve patient outcomes. Therefore, this invited review will review and discuss recent advances in studying the sex-specific physiological mechanisms that affect the renin-angiotensin system and contribute to blood pressure control. It will also discuss research on sex differences in hypertension management, treatment, and outcomes.
RESUMEN
The sodium (Na+)/hydrogen (H+) exchanger 3 (NHE3) is one of the most important Na+/H+ antiporters in the small intestines of the gastrointestinal tract and the proximal tubules of the kidney. The roles of NHE3 in the regulation of intracellular pH and acid-base balance have been well established in cellular physiology using in vitro techniques. Localized primarily on the apical membranes in small intestines and proximal tubules, the key action of NHE3 is to facilitate the entry of luminal Na+ and the extrusion of intracellular H+ from intestinal and proximal tubule tubular epithelial cells. NHE3 is, directly and indirectly, responsible for absorbing the majority of ingested Na+ from small and large intestines and reabsorbing >50% of filtered Na+ in the proximal tubules of the kidney. However, the roles of NHE3 in the regulation of proximal tubular Na+ transport in the integrative physiological settings and its contributions to the basal blood pressure regulation and angiotensin II (Ang II)-induced hypertension have not been well studied previously due to the lack of suitable animal models. Recently, novel genetically modified mouse models with whole-body, kidney-specific, or proximal tubule-specific deletion of NHE3 have been generated by us and others to determine the critical roles and underlying mechanisms of NHE3 in maintaining basal body salt and fluid balance, blood pressure homeostasis, and the development of Ang II-induced hypertension at the whole-body, kidney, or proximal tubule levels. The objective of this invited article is to review, update, and discuss recent findings on the critical roles of intestinal and proximal tubule NHE3 in maintaining basal blood pressure homeostasis and their potential therapeutic implications in the development of angiotensin II (Ang II)-dependent hypertension.
RESUMEN
OBJECTIVE: To explore the relationship between fasting plasma level of total homocysteine (tHcy) and mild cognitive impairment in senile patients with type 2 diabetes mellitus. METHODS: A total of 88 senile type 2 diabetics with mild cognitive impairment treated at our hospital from July 2008 to November 2010 were recruited into the MCI group while 52 senile type 2 diabetics into the DNC group. And the control group was composed of 36 healthy elders. The parameters of tHcy, total glyceride (TG), total cholesterol (TC), low density lipoprotein-C (LDL-C), high density lipoprotein-C (HDL-C), creatinine (Cr), hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), 2 h plasma glucose (2 hPG), fasting insulin (FINS), homeostasis model of insulin resistance (HOMA-IR), folic acid (FA) and vitamin B(12) (VitB(12)) were detected. RESULTS: The patients had a higher level of tHcy in the MCI group than those in the NCM and control groups [(11.3 ± 1.8) vs (9.8 ± 1.5) and (8.1 ± 1.1) µmol/L; P < 0.01]. ROC curve showed that tHcy level had some value of predicting the occurrence of mild cognitive impairment in senile patients with type 2 diabetes mellitus (AUC 0.825, 95%CI 0.758-0.893, P < 0.01). Logistic regression analysis showed that tHcy, SBP, HbA1c, 2 h PG, FINS, LDL-C, HOMA-IR, FA and VitB(12) [OR value: 3.64, 1.68, 1.10, 1.05, 0.81, 1.42, 0.83, 0.74, 0.86 (P < 0.05 or 0.01)] were independent risk factors of mild cognitive impairment in senile diabetic patients. CONCLUSION: Such factors as tHcy, SBP, HbA1c, FPG, 2 hPG, FINS, LDL-C, HOMA-IR, FA and VitB(12) induce senile patients with type 2 diabetes mellitus to suffer mild cognitive impairment. But tHcy level may play an important role in senile diabetic patients with mild cognitive impairment.
Asunto(s)
Trastornos del Conocimiento/etiología , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/psicología , Homocisteína/sangre , Anciano , Femenino , Hemoglobina Glucada/análisis , Humanos , Insulina/sangre , Resistencia a la Insulina , MasculinoRESUMEN
Hypertension is well recognized to be the most important risk factor for cardiovascular diseases, stroke, and end-stage kidney failure. A quarter of the world's adult populations and 46% of the US adults develop hypertension and currently require antihypertensive treatments. Only 50% of hypertensive patients are responsive to current antihypertensive drugs, whereas remaining patients may continue to develop cardiovascular, stroke, and kidney diseases. The mechanisms underlying the poorly controlled hypertension remain incompletely understood. Recently, we have focused our efforts to uncover additional renal mechanisms, pathways, and therapeutic targets of poorly controlled hypertension and target organ injury using novel animal models or innovative experimental approaches. Specifically, we studied and elucidated the important roles of intratubular, intracellular, and mitochondrial angiotensin II (Ang II) system in the development of Ang II-dependent hypertension. The objectives of this invited article are to review and discuss our recent findings that (a) circulating and intratubular Ang II is taken up by the proximal tubules via the (AT1) AT1a receptor-dependent mechanism, (b) intracellular administration of Ang II in proximal tubule cells or adenovirus-mediated overexpression of an intracellular Ang II fusion protein selectively in the mitochonria of the proximal tubules induces blood pressure responses, and (c) genetic deletion of AT1 (AT1a) receptors or the Na+/H+ exchanger 3 selectively in the proximal tubules decreases basal blood pressure and attenuates Ang II-induced hypertension. These studies provide a new perspective into the important roles of the intratubular, intracellular, and mitochondrial angiotensin II/AT1 (AT1a) receptor signaling in Ang II-dependent hypertensive kidney diseases.
RESUMEN
Viciamingyueshanensis, a new species from the Mingyue Mountain Region of western Jiangxi, China, is described and illustrated. It is a perennial climbing liana that always links to riparian woods. A morphological comparison indicated that the new species is closely similar to Viciataipaica K. T. Fu and Viciadichroantha Diels; however, it differs from the other two species by several salient characters, such as plant indumentum, stipule shape, corolla colour, bractlet shape and calyx shape. Photographs, a preliminary conservation assessment, table of morphological characters and distribution map comparing this new species to two morphologically-similar species are also provided.
RESUMEN
PURPOSE: This study aimed to examine pathogenic mutation within one Chinese family of five-generations suffering from autosomal dominant cataract. METHODS: Next-generation sequencing and Sanger sequencing were used to find the pathogenic variants. RESULTS: A rare mutation, c.563G > A, in CRYBB2 gene was found in the proband that showed symptom of non-syndromic congenital autosomal dominant cataract. This mutation had been found in all affected individuals and in one healthy infant, but it did not exist between two individuals who did not develop such disease in that family, as well as in 100 healthy subjects who showed no relation with that family. Cataracts in this family varied with different severity of lens opacities and elongation of axial length. CONCLUSION: One missense mutation c.563G > A is reported in the CRYBB2 gene among one Chinese family suffering from early-onset cataract, and associated novel phenotypes are the elongation of axial length and the types of cataract. Our results expand the spectrum of associated phenotypes of CRYBB2 mutation.
Asunto(s)
Catarata , Cadena B de beta-Cristalina , Pueblo Asiatico/genética , Catarata/genética , China/epidemiología , Análisis Mutacional de ADN , Genes Dominantes , Humanos , Mutación , Mutación Missense , Linaje , Cadena B de beta-Cristalina/genéticaRESUMEN
[Figure: see text].
Asunto(s)
Angiotensina II/metabolismo , Presión Sanguínea/fisiología , Hipertensión/metabolismo , Túbulos Renales Proximales/metabolismo , Receptor de Angiotensina Tipo 1 , Intercambiador 3 de Sodio-Hidrógeno/metabolismo , Animales , Modelos Animales de Enfermedad , Técnicas de Inactivación de Genes/métodos , Tasa de Filtración Glomerular , Ratones , Natriuresis/fisiología , Receptor de Angiotensina Tipo 1/genética , Receptor de Angiotensina Tipo 1/metabolismo , Transducción de SeñalRESUMEN
AIM: To explore the effect of neferine on angiotensin II (Ang II)-induced vascular smooth muscle cell (VSMC) proliferation. METHODS: Human umbilical vein smooth muscle cells (HUVSMCs) were used. Cell proliferation was determined by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry analysis. Heme oxygenase (HO)-1 protein expression was tested by Western blot analysis. Extracellular signal-regulated protein kinase 1/2 (ERK1/2) activation was determined by using immunoblotting. RESULTS: Pre-incubation of HUVSMCs with neferine (0.1, 0.5, 1.0, and 5.0 micromol/L) significantly inhibited Ang II-induced cell proliferation in a concentration-dependent manner and neferine 5.0 micromol/L increased HO-1 expression by 259% compared with control. The antiproliferative effect of neferine was significantly attenuated by coapplication of zinc protoporphyrin IX (ZnPP IX, an HO-1 inhibitor) with neferine. Ang II-enhanced ERK1/2 phosphorylation was markedly reversed by neferine. By inhibiting HO-1 activity with ZnPP IX, the inhibitive effect of neferine on ERK1/2 phosphorylation was significantly attenuated. Cobalt-protoporphyrin (CoPP), an HO-1 inducer, significantly decreased Ang II-induced ERK1/2 phosphorylation and inhibited Ang II-induced cell proliferation. The ERK1/2 pathway inhibitor PD98059 significantly blocked Ang II-enhanced ERK1/2 phosphorylation and inhibited cell proliferation. CONCLUSION: These findings suggest that neferine can inhibit Ang II-induced HUVSMC proliferation by upregulating HO-1, leading to the at least partial downregulation of ERK1/2 phosphorylation.
Asunto(s)
Angiotensina II/farmacología , Bencilisoquinolinas/farmacología , Proliferación Celular/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Hemo-Oxigenasa 1/metabolismo , Músculo Liso Vascular/efectos de los fármacos , Miocitos del Músculo Liso/efectos de los fármacos , Western Blotting , Cardiotónicos/farmacología , Línea Celular , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Humanos , Músculo Liso Vascular/citología , Músculo Liso Vascular/enzimologíaRESUMEN
The ultraviolet light induced absorption change (UV-LIA) of nearly stoichiometric LiNbO3 : Fe : Mn crystals was investigated. The experimental results show that the UV-LIA coefficient change of LiNbO3 : Fe : Mn crystal is not large for congruent sample, increases with increasing Li2 O concentration, reaches the maximum 4. 2 cm(-1) at about 49.57 mol% Li2 O, and then decreases with further increasing Li2 O content. Because the UV-LIA change has a direct relationship with the nonvolatile holographic sensitivity, the experimental results indicate that the nearly stoichiometric LiNbO3 : Fe : Mn crystal with 49.57 mol% Li2 O is the appropriate candidate material for the nonvolatile holographic storage. The visible light induced bleaching results also prove that the suitable composition is 49.57 mol%. With the increase in Li2 O concentration in the LiNbO3 : Fe : Mn crystal, the amount of the bipolaron increases. Bipolarons may be dissociated either optically or thermally so that metastable small polarons are formed. The energy level for biopolaron and small polaron is at about 2.5 and 1.6 eV respectively. When the Li2 O concentration continues to increase, the small polarons are dominating intrinsic defects. The bipolarons have stronger photorefractive capability than the small polarons. The amount of bipolaron is the most with 49.57 mol% Li2 O concentration in the LiNbO3 : Fe : Mn crystal. Based on these experimental results, a three-photorefractive-centers model in nearly stoichimetric LiNbO3 : Fe : Mn crystal is suggested: besides Fe2+/Fe3+ and Mn2+ /Mn3+, bipolarons/small polarons are considered as the third photoactive center.