RESUMEN
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an immune-mediated neuropathy. First-line treatments for CIDP include corticosteroids, intravenous immunoglobulin, and plasma exchange. However, the application is always limited by high costs, effectiveness, and adverse events. This study investigated a new potentially effective and safe therapeutic treatment to alleviate CIDP symptoms and improve the quality of life. In the present case, a 47-year-old rural woman presented with weakness and numbness of progressive extremities. She was diagnosed with CIDP based on abnormal cerebrospinal fluid and electromyography. The patient was treated with intravenous dexamethasone for 1 week and with Huangqi-Guizhi-Wuwu and Bu-Yang-Huan-Wu decoctions for 90 days. Surprisingly, after the treatment, the weakness and numbness were eliminated, and the quality of life improved. The varying INCAT, MRC, and BI scores also reflected the treatment effects. After 8 months of discharge, the symptoms did not relapse during the follow-up. We also searched "traditional Chinese medicine (TCM)" and "CIDP" in PubMed, EMBASE, the Web of Science, the Cochrane Library, the Chinese National Knowledge Infrastructure Databases, Wanfang Data, and the Chongqing Chinese Science and Technology Periodical Database. Finally, only ten studies were included in the literature review. Three studies were randomized controlled trials, and seven were case reports or case series. There were 419 CIDP patients, but all study sites were in China. Nine TCM formulas involving 44 herbs were reported, with Huang Qi (Astragalus membranaceus) being the most important herb. In conclusion, the case and literature demonstrated that TCM treatment might be a more effective, low-cost, and safe option for treating CIDP. Although these preliminary findings are promising, a larger sample size and higher-quality randomized clinical trials are urgently required to confirm our findings.
RESUMEN
Cardiac fibrosis is the main pathological basis of diabetic cardiomyopathy (DCM), and endothelial-to-meschenymal transition (EndMT) is a key driver to cardiac fibrosis and plays an important role in the pathogenesis of DCM. Asymmetric dimethylarginine (ADMA), a crucial pathologic factor in diabetes mellitus, is involved in organ fibrosis. This study aims to evaluate underlying mechanisms of ADMA in DCM especially for EndMT under diabetic conditions. A diabetic rat model was induced by streptozotocin (STZ) injection, and human cardiac microvascular endothelial cells (HCMECs) were stimulated with high glucose to induce EndMT. Subsequently, the role of ADMA in EndMT was detected either by exogenous ADMA or by over-expressing dimethylarginine dimethylaminohydrolase 1 (DDAH1, degradation enzyme for ADMA) before high glucose stimulation. Furthermore, the relationships among forkhead box protein O1 (FoxO1), DDAH1 and ADMA were evaluated by FoxO1 over-expression or FoxO1 siRNA. Finally, we examined the roles of LncRNA DANCR in FoxO1/DDAH1/ADMA pathway and EndMT of HCMECs. Here, we found that EndMT in HCMECs was induced by high glucose, as evidenced by down-regulated expression of CD31 and up-regulated expression of FSP-1 and collagen â . Importantly, ADMA induced EndMT in HCMECs, and over-expressing DDAH1 protected from developing EndMT by high glucose. Furthermore, we demonstrated that over-expression of FoxO1-ADA with mutant phosphorylation sites of T24A, S256D, and S316A induced EndMT of HCMECs by down-regulating of DDAH1 and elevating ADMA, and that EndMT of HCMECs induced by high glucose was reversed by FoxO1 siRNA. We also found that LncRNA DANCR siRNA induced EndMT of HCMECs, activated FoxO1, and inhibited DDAH1 expression. Moreover, over-expression of LncRNA DANCR could markedly attenuated high glucose-mediated EndMT of HCMECs by inhibiting the activation of FoxO1 and increasing the expression of DDAH1. Collectively, our results indicate that LncRNA DANCR deficiency promotes high glucose-induced EndMT in HCMECs by regulating FoxO1/DDAH1/ADMA pathway.
Asunto(s)
Células Endoteliales , ARN Largo no Codificante , Animales , Humanos , Ratas , Amidohidrolasas/genética , Amidohidrolasas/metabolismo , Arginina/metabolismo , Células Endoteliales/metabolismo , Fibrosis , Proteína Forkhead Box O1/genética , Proteína Forkhead Box O1/metabolismo , Glucosa/farmacología , ARN Largo no Codificante/genética , Transducción de SeñalRESUMEN
Objective: To investigate the association between diffusion tensor imaging (DTI) findings and domain-specific cognitive impairment in cerebral small vessel disease (CSVD). Methods: Databases such as PubMed, Excerpta Medical Database (EMBASE), Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure Databases (CNKI), Wanfang, Chinese Biomedical Literature Database (SinoMed), and Chongqing Chinese Science and Technology Periodical Database (VIP) were comprehensively retrieved for studies that reported correlation coefficients between cognition and DTI values. Random effects models and meta-regression were applied to account for heterogeneity among study results. Subgroup and publication bias analyses were performed using Stata software. Results: Seventy-seven studies involving 6,558 participants were included in our meta-analysis. The diagnosis classification included CSVD, white matter hyperintensities (WMH), subcortical ischemic vascular disease, cerebral microbleeding, cerebral amyloid angiopathy (CAA), cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), and Fabry disease. The pooled estimates showed that the fractional anisotropy (FA)-overall exhibited a moderate correlation with general cognition, executive function, attention, construction, and motor performance (r = 0.451, 0.339, 0.410, and 0.319), and the mean diffusitivity/apparent diffusion coefficient (MD/ADC)-overall was moderately associated with general cognition, executive function, and memory (r = -0.388, -0.332, and -0.303, respectively; p s < 0.05). Moreover, FA in cingulate gyrus (CG), cerebral peduncle (CP), corona radiata (CR), external capsule (EC), frontal lobe (FL), fornix (FOR), internal capsule (IC), and thalamic radiation (TR) was strongly correlated with general cognition (r = 0.591, 0.584, 0.543, 0.662, 0.614, 0.543, 0.597, and 0.571), and a strong correlation was found between MD/ADC and CG (r = -0.526), normal-appearing white matter (NAWM; r = -0.546), and whole brain white matter (WBWM; r = -0.505). FA in fronto-occipital fasciculus (FOF) (r = 0.523) and FL (r = 0.509) was strongly associated with executive function. Only MD/ADC of the corpus callosum (CC) was strongly associated with memory (r = -0.730). Besides, FA in CG (r = 0.532), CC (r = 0.538), and FL (r = 0.732) was strongly related to the attention domain. Finally, we found that the sample size, etiology, magnetic resonance imaging (MRI) magnet strength, study type, and study quality contributed to interstudy heterogeneity. Conclusion: Lower FA or higher MD/ADC values were related to more severe cognitive impairment. General cognition and executive function domains attracted the greatest interest. The FL was commonly examined and strongly associated with general cognition, executive function, and attention. The CC was strongly associated with memory and attention. The CG was strongly related to general cognition and attention. The CR, IC, and TR were also strongly related to general cognition. Indeed, these results should be validated in high-quality prospective studies with larger sample sizes. Systematic review registration: http://www.crd.york.ac.uk/PROSPERO, identifier: CRD42021226133.
RESUMEN
Heparin has been documented to reduce myocardial injury caused by ischemia/reperfusion (I/R), but its clinical application is limited due to its strong intrinsic anticoagulant property. Some desulfated derivatives of heparin display low anticoagulant activity and may have potential value as therapeutic agents for myocardial I/R injury. In this study, we observed that 6-O-desulfated heparin, a desulfated derivative of heparin, shortened the activated partial thromboplastin time and exhibited lower anticoagulant activity compared with heparin or 2-O-desulfated heparin (another desulfated derivative of heparin). Then, we explored whether 6-O-desulfated heparin could protect against myocardial I/R injury, and elucidated its possible mechanisms. Administration of 6-O-desulfated heparin significantly reduced creatine kinase activity, myocardial infarct size and cell apoptosis in mice subjected to 30 min of myocardial ischemia following 2 h of reperfusion, accompanied by a reverse in miR-199a-5p elevation, klotho downregulation and reactive oxygen species (ROS) accumulation. In cultured H9c2 cells, the mechanism of 6-O-desulfated heparin against myocardial I/R injury was further explored. Consistent with the results in vivo, 6-O-desulfated heparin significantly ameliorated hypoxia/reoxygenation-induced injury, upregulated klotho and decreased miR-199a-5p levels and ROS accumulation, and these effects were reversed by miR-199a-5p mimics. In conclusion, these results suggested that 6-O-desulfated heparin with lower anticoagulant activity attenuated myocardial I/R injury through miR-199a-5p/klotho and ROS signaling. Our study may also indicate that 6-O-desulfated heparin, as an excellent heparin derivative, is a potential therapeutic agent for myocardial I/R injury.
Asunto(s)
Heparina , Proteínas Klotho , MicroARNs , Daño por Reperfusión Miocárdica , Animales , Ratones , Apoptosis , Modelos Animales de Enfermedad , Heparina/farmacología , Heparina/uso terapéutico , Proteínas Klotho/metabolismo , MicroARNs/genética , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Daño por Reperfusión Miocárdica/metabolismo , Transducción de SeñalRESUMEN
Introduction: Stroke is the first leading cause of mortality and disability worldwide, and post-stroke spasticity (PSS) is the common complication of stroke. Sangdantongluo Granule (Z20210481000), a modern patent Chinese medicine, is widely used in clinical practice to treat PSS. Whereas, there is limited evidence of effectiveness for Sangdantongluo Granule to treat PSS. This study will evaluate the clinical efficacy and safety of Sangdantongluo granule in the treatment of PSS. Methods: and Analysis This multicenter, randomized, double-blind and placebo-controlled study will recruit 132 participants in China who develops PSS 15 days-90 days after stroke. Participants will be randomly assigned in an equal ratio to receive either Sangdantongluo granule or placebo for 2 months twice a day orally. The primary measure is the Modified Ashworth Scale (MAS), Secondary outcome measures include Composite Spasticity Scale (CSS), Simplified Fugl-Meyer Motor Scale (S-FM), National Institute of Health stroke scale (NIHSS), Modified Rankin Scale (mRS), Modified Barther Index (MBI), and Surface electromyography. Adverse events will be supervised throughout the trial. SPSS V. 26.0 statistical software will be used for statistical analysis. Enrolment will be started in April 2022. Ethics and dissemination: The trial and protocol were approved by the Ethics Committee of Hunan Academy of Chinese Medicine Affiliated Hospital (No. [202102]20). We will report the results of this trial in a peer-reviewed journal. Trial registration: ClinicalTrials.gov ChiCTR2100044544. Registered on 23 March 2021.
RESUMEN
Diabetes mellitus is one of the top four leading causes of death among noncommunicable diseases worldwide, according to the World Hibiscus sabdariffa 2019. Roselle (Hibiscus sabdariffa L.), a traditional herbal medicine, has shown significant clinical anti-hyperglycemic efficacy. However, the mechanism of the treatment is not yet clear. We found that Roselle has a certain protective effect on vascular endothelial cells through this study. This study was based on network pharmacology and experimental validation. The present study made a comprehensive analysis by combining active ingredient screening, target prediction and signaling pathway analysis to elucidate the active ingredients and possible molecular mechanism of roselle for the first time, which provided theoretical and experimental basis for the development and application of roselle as an antidiabetic drug.
Asunto(s)
Hibiscus , Células Endoteliales , Hipoglucemiantes/farmacología , Hipoglucemiantes/uso terapéutico , Farmacología en Red , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéuticoRESUMEN
INTRODUCTION: Cognitive impairment is the main clinical manifestation of cerebral small vessel disease (CSVD). However, the mechanism and structural damage in different domains of cognitive disorders are poorly understood. There is an urgent need to quantify the relation between diffusion tensor imaging (DTI) data and impaired cognitive testing in CSVD, which may help to find biomarkers for early diagnosis or treatment evaluation. We aim to summarise the understanding of association between DTI findings and domain-specific cognitive impairment. METHODS AND ANALYSIS: PubMed, EMBASE, Web of science, Cochrane library, Chinese National Knowledge Infrastructure Databases, Wanfang, SinoMed and VIP will be searched, from 1 January 1994 to 1 August 2021. The ClinicalTrials.gov and Chictr.org.cn records will also be searched to identify further potential studies. The included studies should report fractional anisotropy and/or and mean diffusivity/apparent diffusion coefficient data for one or more individual regions of interest in DTI analysis. Meanwhile, cognitive testing scores are also needed. This systematic review will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The quality of cohort or case-control studies will be evaluated by the Newcastle-Ottawa Scale, and the cross-section studies will be evaluated by Agency for Healthcare Research and Quality scale. Meta-analysis, subgroup and sensitivity analyses, and publication bias will be all performed with Stata. ETHICS AND DISSEMINATION: Patients and the public will not be involved in this study. The existing data from published studies will be used. The findings from this research will be relevant information regarding the association of DTI metrics with cognitive disorder, which will be published in a peer-reviewed journal. If we need to amend this protocol, we will give the date of each amendment, describe the change and give the rationale. Changes will not be incorporated into the protocol. PROSPERO REGISTRATION NUMBER: CRD42021226133.
Asunto(s)
Enfermedades de los Pequeños Vasos Cerebrales , Disfunción Cognitiva , Enfermedades de los Pequeños Vasos Cerebrales/diagnóstico por imagen , Disfunción Cognitiva/diagnóstico por imagen , Imagen de Difusión Tensora , Humanos , Metaanálisis como Asunto , Proyectos de Investigación , Revisiones Sistemáticas como AsuntoRESUMEN
OBJECTIVE: K+-Cl- cotransporter-2 (KCC2), which primarily extrudes chloride in mature neurons, triggers hemiplegia limb spasticity after ischemic stroke by affecting neuronal excitability. Our previous study revealed that the Chinese herb Baishaoluoshi Decoction decreases hemiplegia limb spasticity in poststroke spasticity (PSS) patients. This study aimed at elucidating on the effects of Baishaoluoshi Decoction on the BDNF/TrKB-KCC2 pathway in PSS rat models. METHODS: Middle cerebral artery occlusion (MCAO) was adopted for the establishment of PSS rat models. Muscle tension was evaluated by Modified Ashworth Scale. Nissl staining and transmission electron microscopy were used to measure the protective effects of Baishaoluoshi Decoction on ischemic injury-induced neuronal damage due to MCAO. Expression levels of BDNF, TrKB, and KCC2 in brain tissues around the infarct and brainstem were detected by immunohistochemical staining. RESULTS: It was found that Baishaoluoshi Decoction suppressed hemiplegia limb spasticity and alleviated the damage in neurons and synapses in PSS rat models. Importantly, the expression of BDNF, TrKB, and KCC2 in brain tissues around the infarct and brainstem were significantly upregulated after treatment with low-dose and high-dose Baishaoluoshi Decoction. CONCLUSION: Suppression of spasticity by Baishaoluoshi Decoction in PSS rat models may be correlated with upregulated BDNF/TrKB-KCC2 pathway, which may be a complementary therapeutic strategy for PSS.
Asunto(s)
Encéfalo/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Accidente Cerebrovascular Isquémico/complicaciones , Espasticidad Muscular/etiología , Animales , Encéfalo/patología , Factor Neurotrófico Derivado del Encéfalo/efectos de los fármacos , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Masculino , Ratas , Ratas Sprague-Dawley , Receptor trkB/efectos de los fármacos , Receptor trkB/metabolismo , Transducción de Señal/efectos de los fármacos , Simportadores/efectos de los fármacos , Simportadores/metabolismo , Cotransportadores de K ClRESUMEN
Endothelial cell dysfunction is a prominent feature of diabetic cardiovascular complications, and endothelial cell senescence is considered to be an important contributor to endothelial dysfunction. Discoidin domain receptor 1 (DDR1) has been reported to be involved in atherogenesis and cerebral ischemia/reperfusion injury. In this study, we aimed to explore the role of DDR1 in endothelial cell senescence under diabetic conditions and elucidate the underlying mechanisms. A diabetic rat model was established by a single intraperitoneal injection of streptozocin (STZ) (60 mg/kg), which showed an increase in senescence-associated ß-galactosidase (SA-ß-gal) staining signal of thoracic aortic endothelium, impaired vascular structure and function, accompanied by an up-regulation of DDR1. Next, we verified the role of DDR1 in endothelial senescence and the underlying mechanisms in high glucose-treated human umbilical vein endothelial cells (HUVECs). Consistent with the in vivo findings, high glucose induced endothelial senescence, impaired endothelial function and elevated DDR1 expression, accompanied by the elevation of senescence-related genes p53 and p21 expression, and these effects were reversed by DDR1 siRNA. DDR1 has been documented to be a potential target of miR-199a-3p. Here, we found that miR-199a-3p was down-regulated by high glucose in the aorta tissue and HUVECs, while miR-199a-3p mimic significantly suppressed increased endothelial senescence and elevated DDR1 induced by high glucose. In conclusion, our data demonstrated that miR-199a-3p/DDR1/p53/p21 signaling pathway was involved in endothelial senescence under diabetic conditions, and therapeutic targeting DDR1 would be exploited to inhibit endothelial senescence owing to high glucose exposure.
Asunto(s)
Receptor con Dominio Discoidina 1 , MicroARNs , Animales , Senescencia Celular , Células Endoteliales de la Vena Umbilical Humana , Humanos , Ratas , Transducción de SeñalRESUMEN
BACKGROUND: Chinese medicine Sangbaipi decoction is extensively applied to the therapy of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in China. However, owing to the low quality, small sample size, and methodological heterogeneity of these studies, this conclusion is not convincing. Consequently, it is necessary to systematically evaluate the clinical efficacy and safety of Sangbaipi Decoction in the treatment of AECOPD patients, and provide high-quality evidence for its clinical application. METHODS: We will follow the preferred reporting items for systematic review and meta-analysis (PRISMA) for reporting the results of the review in this study. We will utilize the Review Manage software V5.3.0 (The Nordic Cochrane Center, The Cochrane Collaboration, 2014, Copenhagen, Denmark) to assess the risk of bias and visualize the results. We will use Stata software (version 15.0, StataCorp, College Station, TX) to perform the meta-analysis. ETHICS AND DISSEMINATION: This study is a systematic review and meta-analysis protocol of Sangbaipi decoction on AECOPD, participants were not recruited and data were not collected from participants, so ethical ratification is not required. RESULTS: This study will provide high-quality synthesis of the effectiveness and safety of Sangbaipi decoction for AECOPD. Upon completion, the results will be submitted to a peer-reviewed journal. CONCLUSION: The efficacy and safety assessment of Sangbaipi decoction for AECOPD will be supported by this protocol. REGISTRATION NUMBER: PROSPERO CRD 42019138405.
Asunto(s)
Medicamentos Herbarios Chinos/farmacología , Medicina Tradicional China/métodos , Morus , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Metaanálisis como Asunto , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Proyectos de Investigación , Brote de los Síntomas , Revisiones Sistemáticas como Asunto , Resultado del TratamientoRESUMEN
Control of photoinduced electron transfer through selective excitation of a π-conjugated diblock oligomeric system featuring tetrathiophene (T4) and tetra(phenylene ethynylene) (PE4) donor blocks capped with a naphthalene diimide (NDI) acceptor (T4PE4NDI) is demonstrated. Each π-conjugated oligomeric segment has its own discrete ionization potential, electron affinity, and optical band gap which provides an absorption profile that has specific wavelengths that offer selective excitation of the PE4 and T4 blocks. Therefore, T4PE4NDI can be selectively excited to form a charge-separated state via ultrafast photoinduced electron transfer from the PE4 segment to NDI when excited at 370 nm, but it does not produce a charge-separated state when excited at 420 nm (T4). Picosecond transient absorption techniques were performed to probe the excited-state dynamics, revealing ultrafast charge separation (â¼4 ps) occurring from the PE4 segment to NDI when excited at 370 nm, followed by delocalization of the hole over the T4 segment. On the contrary, electron transfer is suppressed with excitation at longer wavelengths (≥420 nm), where the spectrum is dominated by the T4 unit. The rate of electron transfer and charge recombination was investigated versus the length of the PE bridge unit in oligomers featuring zero and two PE units (T4NDI and T4PE2NDI). The rate of charge recombination decreases from 1.2 × 1011 to 1.0 × 109 s-1 with increasing bridge length between the T4 and NDI components (T4NDI to T4PE4NDI). Furthermore, wavelength-dependent photoinduced electron transfer was not observed in either T4NDI or T4PE2NDI due to an insufficient PEn bridge length. This work demonstrates the ability to use optical wavelength to control photoinduced electron transfer in a fully π-conjugated oligomer.
RESUMEN
Blood-retinal barrier breakdown is the main pathological characteristics of diabetic retinopathy (DR). Asymmetric dimethylarginine (ADMA) was reported to be elevated in DR patients. In this study, we observed the dynamic profile of ADMA, retinal morphology and permeability of BRB at 2, 4 or 8 week of diabetic rats induced by a single intraperitoneal injection of streptozocin (60 mg/kg) and in cultured rat retinal pericytes pretreated with D-glucose (30 mM) for 1, 3, 5 and 7 days or ADMA (3, 10, 30 µM) for 24, 48 and 72 h, trying to explore the effects of ADMA on blood-retinal barrier in DR. Gap junction intercellular communication (GJIC) and the expression of blood-retinal barrier-specific component connexin 43 (Cx43) were examined in diabetic rats or cultured retinal pericytes to elucidate whether ADMA impacted blood-retinal barrier function via damaging Cx43-GJIC. The results showed that with increasing duration of diabetes, the ultrastructure of blood-retinal barrier of diabetic rats appeared cell junction damage, apoptosis of retinal pericytes and breakdown of barrier successively. The increases in retinal permeability, ADMA levels and Cx43 expression, and abnormal GJIC were observed in diabetic rats and retinal pericytes exposed to D-glucose (30 mM). A glucose-like effect was seen using ADMA or another L-arginine analogue NG-monomethyl-L-arginine or dimethylarginine dimethylaminohydrolases (DDAHs) siRNA, implicating that ADMA aggravated the breakdown of blood-retinal barrier via damaging Cx43-GJIC.
Asunto(s)
Arginina/análogos & derivados , Barrera Hematorretinal/patología , Diabetes Mellitus Experimental/patología , Retinopatía Diabética/patología , Pericitos/patología , Animales , Apoptosis , Arginina/metabolismo , Barrera Hematorretinal/metabolismo , Comunicación Celular , Permeabilidad de la Membrana Celular , Células Cultivadas , Conexina 43/metabolismo , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/metabolismo , Retinopatía Diabética/inducido químicamente , Retinopatía Diabética/metabolismo , Uniones Comunicantes/patología , Glucosa/metabolismo , Masculino , Pericitos/metabolismo , Ratas , Ratas Sprague-Dawley , Estreptozocina/administración & dosificación , Estreptozocina/toxicidadRESUMEN
Fibrosis is a reparative process with very few therapeutic options to prevent its progression to organ dysfunction. Chronic fibrotic diseases contribute to an estimated 45% of all death in the industrialized world. Asymmetric dimethylarginine (ADMA), an endothelial nitric oxide synthase inhibitor, plays a crucial role in the pathogenesis of various cardiovascular diseases associated with endothelial dysfunction. Recent reports have focused on ADMA in the pathogenesis of tissue fibrosis. This review discusses the current knowledge about ADMA biology, its association with risk factors of established fibrotic diseases and the potential pathophysiological mechanisms implicating ADMA in the process of tissue fibrosis.
Asunto(s)
Arginina/análogos & derivados , Fibrosis/metabolismo , Animales , Arginina/metabolismo , HumanosRESUMEN
Diabetic retinopathy (DR) is a leading cause of vision loss with retinal neovascularization. This study aims to investigate whether Asymmetric dimethylarginine (ADMA) impacts the pathogenesis of DR via focusing on promoting retinal neovascularization and its underlying molecular mechanisms. Diabetic rats were induced by a single intraperitoneal injection of streptozotocin (STZ) for 20â¯weeks. ADMA levels in aqueous and the influence of hypoxia on ADMA and angiogenesis in RF/6A cells were examined. The effects and underlying molecular mechanisms of ADMA on neovascularization of RF/6A cells were further evaluated by administration of ADMA, DDAH siRNA or ephrinB2 siRNA. Results showed that ADMA levels were elevated in both aqueous from diabetic rats and culture medium in RF/6A cells pretreated with hypoxia. Administration of ADMA directly promoted proliferation, migration, adhesion and tube formation of RF/6A cells, which was further confirmed by DDAH1 siRNA or DDAH2 siRNA. In addition, ephrinB2 expression was increased under diabetic conditions, and the angiogenic effects of ADMA were blocked by ephrinB2 siRNA. In conclusion, ADMA contributes to the neovascularization of retina in diabetic mellitus, which is regulated by ephrinB2.
Asunto(s)
Arginina/análogos & derivados , Diabetes Mellitus Experimental/complicaciones , Retinopatía Diabética/etiología , Células Endoteliales/metabolismo , Efrina-B2/metabolismo , Neovascularización Retiniana/etiología , Vasos Retinianos/metabolismo , Amidohidrolasas/genética , Amidohidrolasas/metabolismo , Animales , Arginina/metabolismo , Hipoxia de la Célula , Línea Celular , Retinopatía Diabética/metabolismo , Retinopatía Diabética/patología , Células Endoteliales/patología , Efrina-B2/genética , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Células Endoteliales de la Vena Umbilical Humana/patología , Humanos , Macaca mulatta , Masculino , Proteína-Arginina N-Metiltransferasas/genética , Proteína-Arginina N-Metiltransferasas/metabolismo , Interferencia de ARN , Ratas Sprague-Dawley , Neovascularización Retiniana/metabolismo , Neovascularización Retiniana/patología , Vasos Retinianos/patología , Transducción de SeñalRESUMEN
A series of π-conjugated oligomer-acceptor dyads were synthesized that feature oligo(phenylene ethynylene) (OPE) conjugated backbones end-capped with a naphthalene diimide (NDI) acceptor. The OPE segments vary in length from 4 to 8 phenylene ethynene units (PEn-NDI, where n = 4, 6 and 8). Fluorescence and transient absorption spectroscopy reveals that intramolecular OPE â NDI charge transfer dominates the deactivation of excited states of the PEn-NDI oligomers. Both charge separation (CS) and charge recombination (CR) are strongly exothermic (ΔG0CS â¼ -1.1 and ΔG0CR â¼ -2.0 eV), and the driving forces do not vary much across the series because the oxidation and reduction potentials and singlet energies of the OPEs do not vary much with their length. Bimolecular photoinduced charge transfer between model OPEs that do not contain the NDI acceptors with methyl viologen was studied, and the results reveal that the absorption of the cation radical state (OPE+â¢) remains approximately constant (λ â¼ 575 nm) regardless of oligomer length. This finding suggests that the cation radical (polaron) of the OPE is relatively localized, effectively occupying a confined segment of n ≤ 4 repeat units in the longer oligomers. Photoinduced intramolecular electron transfer dynamics in the PEn-NDI series was investigated by UV-visible femtosecond transient absorption spectroscopy with visible and mid-infrared probes. Charge separation occurs on the 1-10 ps time scale with the rates decreasing slightly with increased oligomer length (ßCS â¼ 0.15 Å-1). The rate for charge-recombination decreases in the sequence PE4-NDI > PE6-NDI â¼ PE8-NDI. The discontinuous distance dependence in the rate for charge recombination may be related to the spatial localization of the positive polaron state in the longer oligomers.
RESUMEN
A polystyrene-based chromophore-catalyst assembly (poly-2) has been synthesized and assembled at a mesoporous metal oxide photoanode. The assembly contains water oxidation catalyst centers based on [Ru(trpy) (phenq)]2+ (Ru-Cat) and [Ru(bpy)3]2+ derivatives (Ru-C) as chromophores (trpy= 2,2';6,2â³- terpyridine, phenq = 2-(quinol-8'-yl)-1,10-phenanthroline and bpy = 2,2'-bipyridine). The photophysical and electrochemical properties of the polychromophore-oxidation catalyst assembly were investigated in solution and at the surface of mesoporous metal oxide films. The layer-by-layer (LbL) method was utilized to construct multilayer films with cationic poly-2 and anionic poly(acrylic acid) (PAA) for light-driven photochemical oxidations. Photocurrent measurements of (PAA/poly-2)10 LbL films on mesoporous TiO2 demonstrate light-driven oxidation of phenol and benzyl alcohol in aqueous solution. Interestingly, illumination of (PAA/poly-2)5 LbL films on a fluorine doped SnO2/TiO2 core/shell photoanode in aqueous solution gives rise to an initial photocurrent (â¼18.5 µA·cm-2) that is in part ascribed to light driven water oxidation.
RESUMEN
The interactions of two anionic poly(phenylene ethynylene) sulfonate-conjugated polyelectrolytes (mPPESO3- and pPPESO3-) with two alkynylplatinum(II) terpyridine complexes (Pt2+ and Pt3+) were studied. The Pt(II) complexes interact with helical mPPESO3- by intercalation within the polymer helix to form a "guest-host" ensemble. Titration of Pt(II) complexes into an aqueous solution of mPPESO3- gives rise to efficient quenching of the polymer's fluorescence; meanwhile, triplet metal-metal-to-ligand charge transfer (3MMLCT) state emission from the intercalated Pt(II) complexes appears when the ensembles are excited into the polymer's absorption band. The 3MMLCT state emission implies that the Pt(II) complexes aggregate or dimerize on the mPPESO3- scaffold. The responses of the mPPESO3- and Pt(II) complex ensembles to various proteins were examined by monitoring the mPPESO3- fluorescence change. Negatively charged proteins recover the mPPESO3- fluorescence more than the positively charged proteins under physiological pH, indicating that electrostatics play an important role in the protein-ensemble interaction.
Asunto(s)
Polímeros/química , Alcanosulfonatos , Ligandos , Estructura Molecular , ProteínasRESUMEN
BACKGROUND AND OBJECTIVE: Diabetic pulmonary fibrosis is a severe disease that increases mortality risk of diabetes. However, the molecular mechanisms leading to pulmonary fibrosis in diabetes are poorly understood. This study investigated the roles of epithelial-mesenchymal transition (EMT) and the associated molecular mechanisms in streptozotocin (STZ)-induced rat pulmonary fibrosis. METHODS: The rat model of diabetic pulmonary fibrosis was established by intraperitoneal injection of a single dose of STZ (35 mg/kg). Typical lesions of diabetic pulmonary fibrosis were observed 8 weeks after STZ injection by hematoxylin-eosin (HE) and Masson staining. Human bronchial epithelial cells (HBECs) and A549 cells were treated by high glucose. Gene or protein expression was measured by real-time PCR, Western blot, immunohistochemistry or immunofluorescence. The knockdown of lectin-like oxidized low density lipoprotein receptor-1 (LOX-1) or transforming growth factor-ß1 (TGF-ß1) was conducted by siRNA. RESULTS: Activation of EMT was observed in lung tissues of STZ-induced diabetic rats, exhibiting a loss in the epithelial cell marker E-cadherin and an increase in the mesenchymal marker Vimentin. The protein and mRNA levels of LOX-1, TGF-ß1 and krüppel-like factor 6 (KLF6) in the lung tissues were increased. Incubation of HBECs and A549 cells with high glucose activated EMT and induced an increase in LOX-1, TGF-ß1 and KLF-6 expression. LOX-1 siRNA inhibited high glucose-induced EMT in HBECs and A549 cells, which correlated with the reduction of TGF-ß1. TGF-ß1 siRNA decreased the expression of LOX-1 and KLF6. CONCLUSIONS: EMT was involved in the pathological process of diabetic pulmonary fibrosis, which was activated by LOX-1/TGF-ß1/KLF6 signaling pathway.
Asunto(s)
Diabetes Mellitus Experimental/complicaciones , Transición Epitelial-Mesenquimal/fisiología , Pulmón/patología , Fibrosis Pulmonar/etiología , Células A549 , Animales , Western Blotting , Cadherinas/metabolismo , Modelos Animales de Enfermedad , Células Epiteliales/metabolismo , Humanos , Factor 6 Similar a Kruppel/genética , Factor 6 Similar a Kruppel/metabolismo , Pulmón/metabolismo , Ratas , Reacción en Cadena en Tiempo Real de la Polimerasa , Receptores Depuradores de Clase E/genética , Receptores Depuradores de Clase E/metabolismo , Transducción de Señal/fisiología , Estreptozocina , Factor de Crecimiento Transformador beta1/genética , Factor de Crecimiento Transformador beta1/metabolismo , Vimentina/metabolismoRESUMEN
Numerous studies demonstrate that reactive aldehydes are highly toxic and aldehyde dehydrogenase 2 (ALDH2)-mediated detoxification of reactive aldehydes is thought as an endogenous protective mechanism against reactive aldehydes-induced cell injury. This study aims to explore whether lipoic acid, a potential ALDH2 activator, is able to protect gastric mucosa from ethanol-induced injury through a mechanism involving clearance of reactive aldehydes. The rats received 60% of acidified ethanol through intragastric administration and held for 1 h to establish a mucosal injury model. Lipoic acid (10 or 30 mg/kg) or Alda-1 (a positive control, 10 mg/kg) was given 45 min before the ethanol treatment. The gastric tissues were collected for analysis of gastric ulcer index, cellular apoptosis, 4-hydroxy-2-nonenal (4-HNE) and malondialdehyde (MDA) contents, and ALDH2 activity. The results showed that acute administration of ethanol led to an increase in gastric ulcer index, cellular apoptosis, 4-HNE and MDA contents concomitant with a decrease in ALDH2 activity; these phenomena were reversed by lipoic acid or Alda-1. The gastric protection of lipoic acid was attenuated in the presence of ALDH2 inhibitor. Based on these observations, we conclude that lipoic acid exerts the beneficial effects on ethanol-induced injury through a mechanism involving, at least in part, ALDH2 activation. As a dietary supplement or a medicine already in some countries, lipoic acid can be used to treat the ethanol - induced gastric mucosal injury.