RESUMEN
Vascular calcification is very common in clinical. Severe vascular calcification is related to the occurrence of adverse events. Oxidative stress (OS) plays a pathophysiological role in the formation of vascular calcification. Previous studies have demonstrated that fibroblast growth factor 21(FGF21) could inhibit vascular calcification both in vivo and in vitro. FGF21 has also been proved to promote the recovery of superoxide dismutase (SOD) and thereby alleviate OS. Thus, our assumption was that FGF21 inhibit vascular calcification partly by restoring the level of antioxidant SOD and reducing OS. In this study, we established the vascular calcification by 5/6 nephrectomy plus high phosphate diet chronic kidney disease (CKD) model. The results showed the receptor of FGF21, fibroblast growth factor receptor 1 (FGFR1) and ßKlotho in the aorta increased in CKD group, and mainly located in the media of the artery. Ulteriorly, immunofluorescence (IF) and IHC staining showed that FGFR1 and ßKlotho mainly existed in arterial vascular smooth muscle cells (VSMCs). When FGF21 was knock out, the calcification was more severe in FGF21 KO + CKD mice, compared to wild type (WT)+ CKD mice. The transcriptional level of vascular calcification-related genes was significantly higher in FGF21 KO mice than control group. The dihydroethidium (DHE) staining reactive oxygen species (ROS) level in the CKD group was higher compared to the control group, but lower in FGF21 KO + CKD group, and the transcriptional level of SOD1 and SOD2 in FGF21 KO + CKD group was significantly higher than that in CKD group. In conclusion, FGF21 could inhibit vascular calcification, partly by restoring the level of antioxidant SOD and reducing vascular oxidative stress. This study provides further evidence for FGF21 as a candidate drug for cardiovascular protective agents.
Asunto(s)
Insuficiencia Renal Crónica , Calcificación Vascular , Animales , Ratones , Antioxidantes/metabolismo , Factores de Crecimiento de Fibroblastos/metabolismo , Músculo Liso Vascular/metabolismo , Miocitos del Músculo Liso/metabolismo , Estrés Oxidativo , Insuficiencia Renal Crónica/metabolismo , Superóxido Dismutasa/metabolismo , Calcificación Vascular/metabolismoRESUMEN
Background: Owing to advances in procedural techniques and the training of interventional staff in catheterization labs, recent work has demonstrated the safety of percutaneous coronary intervention (PCI) as a treatment for patients suffering from chronic total occlusion (CTO). However, there has been little research focused on systematic comparisons of PCI outcomes in CTO patients that did or did not exhibit a history of previous coronary artery bypass grafting (CABG). Methods: Electronic databases were systematically searched for all studies comparing CTO-PCI outcomes for patients with and without a history of CABG, with event rates subsequently being compared via random-effects models with forest plots and odds ratios with 95% confidence intervals (CI), owing to the assumption of between-studies heterogeneity. Results: In total, 8 observational studies enrolling 13,509 CTO patients were identified, including 3389 and 10,120 patients with and without a history of prior CABG, respectively. Patients were enrolled in these studies from 1999-2018. Pooled analyses indicated that CABG history was not linked to a lower proportion of radial access 24 (95% CI 0.52-1.03, p = 0.08), and a prior CABG history was linked to a greater contrast volume (95% CI 0.12-0.44, p < 0.001), higher radiation dose (95% CI 0.27-0.40, p < 0.001), longer fluoroscopy time (95% CI 0.42-0.61, p < 0.001), longer procedural time (95% CI 0.38-0.64, p < 0.001), a higher number of implanted stents (95% CI 0.41-0.60, p < 0.001), longer total stent length (95% CI 0.21-0.60, p < 0.001), higher technical failure rates (95% CI 1.46-1.85, p < 0.001), and higher rates of procedural failure (95% CI 1.42-1.79, p < 0.001). The in-hospital mortality (95% CI 1.50-4.03, p < 0.001) and periprocedural mortality (95% CI 1.63-3.73, p < 0.001) of patients with a history of CABG were also higher. While stroke incidence was comparable in both groups (95% CI 0.80-4.47, p = 0.15), periprocedural major adverse cardiovascular and cerebrovascular events (MACCE) rates were significantly higher among patients exhibiting a history of CABG (95% CI 1.66-2.94, p < 0.001). Conclusions: These results suggest that CTO-PCI procedures may be more challenging and associated with lower rates of success in CABG patients relative to procedures performed in patients without any history of CABG. Moreover, in-hospital outcomes including MACCE and mortality were worse for patients that had undergone prior CABG.
RESUMEN
BACKGROUND: Chronic total occlusion (CTO) of the coronary artery is a difficult problem in clinical practice. The triglyceride-glucose (TyG) index is an effective risk predictor of cardiovascular risk. However, the relationship between the TyG index and the prognosis of CTO patients remains unstudied. Thus, the present study aimed to investigate the relationship between the TyG index and cardiovascular risk in CTO patients. METHODS: This was a single-centre, retrospective cohort study. We retrospectively enrolled 652 patients with CTO lesions diagnosed by angiography and who underwent revascularization through PCI. Patients were routinely followed up for 24 months unless meeting the endpoint. The primary endpoint was the composite of all-cause death, nonfatal myocardial infarction, unplanned revascularization, and nonfatal ischaemic stroke. To test the association of the TyG index with cardiovascular risk, the categorized TyG index and Cox proportional hazards regression models were utilized. RESULTS: A total of 652 patients were enrolled in the final analysis (male: 83.7%, age: 58.2 ± 10.49 years). The average TyG index was 8.8 ± 0.57. CTO PCIs were procedurally successfully completed in 503 (77.15%) patients. During the follow-up period of 22.8 ± 3.84 months, 73 (11.19%) major adverse cardiovascular and cerebral events (MACCEs) occurred. When fully adjusted, there was a 2.09-fold risk for MACCEs among patients with the highest TyG index compared with those with the lowest TyG index [T2 vs. T1: hazard ratio (HR) 1.24, 95% confidence interval (CI) 0.65-2.38, P = 0.057; T3 vs. T1: HR 2.09, 95% CI 1.14-3.86, P = 0.018; P for trend = 0.036]. The restricted cubic spline (RCS) analysis showed that the HR for MACCEs increased as the TyG index increased over 8.71 [HR per standard deviation (SD) 1.740, 95% CI 1.23-2.46, P = 0.002]. The risk of MACCEs increased with increasing tertiles of TyG index in successful CTO PCI patients and nondiabetes mellitus (DM) patients (P < 0.05) but not in patients with failed CTO PCI and DM patients. CONCLUSION: The study revealed that the TyG index had significant relevance to cardiovascular risk in CTO patients and suggests that the TyG index is feasible for predicting cardiovascular risk in CTO patients.
Asunto(s)
Isquemia Encefálica , Oclusión Coronaria , Intervención Coronaria Percutánea , Accidente Cerebrovascular , Anciano , Biomarcadores , Glucemia , Isquemia Encefálica/etiología , Oclusión Coronaria/diagnóstico por imagen , Oclusión Coronaria/terapia , Glucosa , Humanos , Masculino , Persona de Mediana Edad , Intervención Coronaria Percutánea/efectos adversos , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Accidente Cerebrovascular/etiología , Factores de Tiempo , TriglicéridosRESUMEN
Background: Several complications can contribute to the risk of shock during the chronic total occlusion (CTO) percutaneous coronary intervention (PCI) procedure. However, some patients that develop shock do not exhibit any apparent complications, and few studies to date have discussed the risk of unexplained perioperative shock in patients undergoing CTO PCI. Accordingly, this study was designed with the goal of defining perioperative risk factors linked to the odds of unexplained shock during CTO PCI. Methods: In total, this study analyzed data from 924 patients that underwent CTO PCI without any in-hospital complications from January 2016-August 2021. Cardiologists collected data pertaining to patient clinical characteristics, laboratory findings, angiographic findings, and procedural characteristics. Patients were separated into two groups based upon whether or not they experienced perioperative shock. The relationship between specific variables and perioperative shock incidence was assessed via a multivariable stepwise logistic regression approach. A risk-scoring nomogram was then designed for use as a tool to guide patient risk assessment efforts during PCI procedural planning. Results: Overall, 4.8% of these patients (44/924) experienced unexplained perioperative shock. Independent predictors associated with unexplained shock during CTO PCI included baseline systolic pressure (odds ratio (OR) 0.968, 95% confidence interval (CI): 0.945-0.991), baseline heart rate (OR 1.055, 95% CI: 1.020-1.091), baseline hemoglobin (OR 0.970, 95% CI: 0.947-0.994), procedure duration (OR 1.008, 95% CI: 1.002-1.015), J-CTO score (OR 1.521, 95% CI: 1.021-2.267), and use of a retrograde approach (OR 3.252, 95% CI: 1.426-7.415). The unbiased C-index estimate was 0.859, and this model exhibited excellent calibration. Conclusions: The risk of unexplained shock is an important consideration for clinicians performing the CTO PCI procedure. These analyses revealed unexplained shock risk to be independently related to lower baseline systolic pressure, higher baseline heart rate, lower baseline hemoglobin, more procedure time, higher J-CTO score, and more use of a retrograde approach.
RESUMEN
Vascular calcification (VC), a significant risk factor of many cardio-cerebral vascular diseases, is a perplexing issue with no effective treatment in clinical work up to now. Endoplasmic reticulum stress (ERS) mediated apoptosis has been proved to be a significant mechanism for initiating VC process. Activating transcription factor 4 (ATF4), a key transcription factor of ERS, is most closely associated with VC. Fibroblast growth factor 21 (FGF21), an atypical member of the FGFs family, has a protective biological function in various metabolic diseases by ERS pathways. However, the possible effects of FGF21 on VC by regulating ERS, especially through the ATF4 pathway, is still unclear. Our research provides the first evidence that exogenous FGF21 treatment can alleviate the vitamin D3 plus nicotine-induced VC at least in part via suppressing ATF4 mediated apoptosis and osteogenic transformation in rats.
Asunto(s)
Factor de Transcripción Activador 4 , Factores de Crecimiento de Fibroblastos , Calcificación Vascular , Factor de Transcripción Activador 4/metabolismo , Animales , Apoptosis , Estrés del Retículo Endoplásmico , Factores de Crecimiento de Fibroblastos/metabolismo , Ratas , Ratas Sprague-Dawley , Calcificación Vascular/tratamiento farmacológico , Calcificación Vascular/metabolismoRESUMEN
Fibroblast growth factor 21 (FGF21) is a growth factor with endocrine function in the fibroblast growth factor family. Previous reports have shown that FGF21 is involved in the regulation of energy metabolism and plays a protective role in cardiovascular diseases such as coronary heart disease, diabetes, non-alcoholic fatty liver disease and so on. Recent studies have found that FGF21 can induce autophagy in a variety of tissues and organs, and autophagy is involved in many pathological processes of cardiovascular diseases, including vascular calcification, atherosclerosis, and myocardial ischemia-reperfusion injury. Therefore, FGF21 may play a protective role in a variety of cardiovascular diseases by regulating autophagy. This article reviews the research progress on the protective role of FGF21 in cardiovascular diseases by inducing autophagy.
Asunto(s)
Autofagia , Enfermedades Cardiovasculares , Factores de Crecimiento de Fibroblastos , Autofagia/genética , Autofagia/fisiología , Enfermedades Cardiovasculares/genética , Enfermedades Cardiovasculares/metabolismo , Factores de Crecimiento de Fibroblastos/genética , Factores de Crecimiento de Fibroblastos/metabolismo , Humanos , Daño por Reperfusión Miocárdica/genética , Daño por Reperfusión Miocárdica/metabolismoRESUMEN
Eculizumab (ECU), a C5 complement inhibitor, is approved to treat acetylcholine receptor autoantibody positive generalized myasthenia gravis (AChR MG). The clinical effect of ECU relies on inhibition of the terminal complement complex; however, the effect of ECU on lymphocytes is largely unknown. We evaluated innate and adaptive immunity among AChR MG patients (N = 3) before ECU and ≥3 months later while on stable therapy, and found reduced activation markers in memory CD4+ T cell subsets, increased regulatory T cell populations, and reduced frequencies of CXCR5+HLA-DR+CCR7+ Tfh subsets and CD11b+ migratory memory B cells. We observed increases within CD8+ T cell subsets that were terminally differentiated and senescent. Our data suggest complement inhibition with ECU modulates the adaptive immunity in patients with MG, consistent with preclinical data showing changes in complement-mediated signaling by T- and antigen-presenting cells. These findings extend our understanding of ECU's mechanism of action when treating patients with MG.
Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Linfocitos B/efectos de los fármacos , Inactivadores del Complemento/uso terapéutico , Miastenia Gravis/tratamiento farmacológico , Linfocitos T/efectos de los fármacos , Inmunidad Adaptativa/efectos de los fármacos , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Miastenia Gravis/inmunologíaRESUMEN
BACKGROUND: Patients with myasthenia gravis (MG) may be particularly vulnerable during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic due to risk of worsening disease during infection, potential adverse impacts of coronavirus disease 2019 (COVID-19) treatments on neuromuscular transmission, and a limited ability to fight off infection related to immunosuppressive treatments. Our goal is to understand how patients are experiencing the COVID-19 pandemic, including where they receive relevant information, how it has affected medical care, and what measures they use to protect themselves. METHODS: This is a prospective online survey study at large academic practice. All patients with a neuromuscular junction disorder diagnosis code in the Duke Health System were invited to participate. RESULTS: One thousand eight hundred and forty eight patients were approached to participate and 75 completed the survey between 16 April 2020 and 28 May 2020. The most frequently used information sources were non-presidential federal government (75%), state government (57%), local healthcare provider (37%), and television news (36%). Non-presidential federal government (80%), local healthcare providers (55%), state government (33%), and patient support organizations (29%) were considered the most trusted information sources. Thirty-three (44%) of survey responders had attended a telemedicine visit. Patients were taking recommended precautions during the pandemic and remained very concerned (69%) about COVID-19. Generalized Anxiety Disorder-7 scores were moderate-severe in 20% of responders. CONCLUSIONS: Healthcare providers, the government, and patient organizations play a critical role in communicating with the MG patient community. Use of targeted messaging strategies by these groups to convey accurate information may increase effectiveness and lead to more informed patients with reduced anxiety.
Asunto(s)
COVID-19 , Conocimientos, Actitudes y Práctica en Salud , Miastenia Gravis , Anciano , Estudios de Cohortes , Gobierno Federal , Femenino , Desinfección de las Manos , Personal de Salud , Humanos , Masculino , Máscaras , Persona de Mediana Edad , Cuestionario de Salud del Paciente , Distanciamiento Físico , Estudios Prospectivos , SARS-CoV-2 , Gobierno Estatal , Encuestas y Cuestionarios , Telemedicina , Televisión , Estados UnidosRESUMEN
Interleukin-17-expressing CD4+ T helper 17 (Th17) cells are considered to be critical regulators of thymic inflammation in AChR-MG patients. However, Th17 cells are functionally heterogeneous and circulating Th17 subsets are incompletely understood in AChR-MG patients. Here, we studied characteristics of Th17 subsets in peripheral blood from treatment-naïve AChR-MG patients, patients treated with immunosuppressants, as well as healthy controls. We found increased frequencies of circulating Th1-like Th17 (Th1/17) (IFN-γ + IL-17 + CD4 + CD3+) cells, which declined earlier than conventional Th17 (IFN-γ - IL-17 + CD4 + CD3+) cells in patients who respond well to immunosuppression treatment. Additionally, circulating Th1/17 cell frequencies were found to correlate positively with disease severity. Further, compared to conventional Th17 cells, Th1/17 cells showed an elevated expression of IFNG, TBX21, IL23R, CSF2, and a reduced expression of AHR and IL10. Taken together, our results suggest circulating Th1/17 cells may serve as a biomarker of disease severity and provide a strong rationale for early intervention in AChR-MG patients.
Asunto(s)
Miastenia Gravis/inmunología , Células TH1/inmunología , Células Th17/inmunología , Adulto , Biomarcadores , Femenino , Humanos , Masculino , Persona de Mediana Edad , Receptores Colinérgicos , Índice de Severidad de la EnfermedadRESUMEN
Although it is well documented that circulating dendritic cells (DCs) have specialized features during many kinds of physiological and pathological conditions, there are few reports about the features of DCs in the peripheral blood of myasthenia gravis (MG) patients. We investigated the quantitative and component features of DCs and their implications in MG. Peripheral blood samples from different kinds of MG patients were collected and their clinical characteristics were recorded. Using flow cytometry, we distinguished circulating DC subsets [plasmacytoid DCs (pDCs) and myeloid DCs (mDCs)] and enumerated their densities in peripheral blood. Absolute numbers of circulating pDCs were significantly decreased in naïve MG patients compared with healthy controls, resulting in a markedly lower ratio of the pDC to mDC percentage in total circulating DCs (pDCs/mDCs), suggesting an imbalance in the proportions of the two main circulating DC subsets. The clinical status of MG patients was improved after drug treatment, together with increased pDCs/mDCs. In a longitudinal follow-up, we observed that circulating mDCs were significantly reduced after 1â¯month of therapy with a corticosteroid and immunosuppressant, resulting in recovery of pDCs/mDCs. Although the exact meaning of the proportion change in circulating DC subsets is unknown, pDCs/mDCs might reflect the balance between the autoimmune response and immune tolerance of a patient. Moreover, changes in pDCs/mDCs during treatment might be a promising marker to predict the efficacy of a specific drug used for MG patients.
Asunto(s)
Células Dendríticas/inmunología , Miastenia Gravis/inmunología , Adolescente , Corticoesteroides/uso terapéutico , Adulto , Anciano , Recuento de Células , Niño , Preescolar , Femenino , Citometría de Flujo , Humanos , Tolerancia Inmunológica/inmunología , Inmunofenotipificación , Inmunosupresores/uso terapéutico , Leflunamida/uso terapéutico , Masculino , Persona de Mediana Edad , Miastenia Gravis/tratamiento farmacológico , Adulto JovenRESUMEN
BACKGROUND: Endomyocardial fibrosis (EMF) is a rare condition and a major cause of death in tropical countries. The etiology of EMF remains elusive, and no specific treatment has been developed yet, therefore it carries poor prognosis. CASE PRESENTATION: An 81-year-old male Chinese patient with a history of long-standing exertional breathlessness, presented with worsening symptoms rapidly evolving to orthopnea. A proper specific treatment was prescribed to the patient in the following days, including diuretics, angiotensin-converting-enzyme inhibitor and beta blockers. The patient died of progressive multiple organ failure. CONCLUSION: Echocardiography is technically limited due to the acoustic shadowing as a result of the calcification. Chest computed tomography is a more accurate diagnostic tool to examine the anatomic distribution and extent of endomyocardial calcification in this rare case.
Asunto(s)
Ecocardiografía , Fibrosis Endomiocárdica/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Anciano de 80 o más Años , Fármacos Cardiovasculares/uso terapéutico , China , Progresión de la Enfermedad , Disnea/etiología , Fibrosis Endomiocárdica/complicaciones , Fibrosis Endomiocárdica/tratamiento farmacológico , Fibrosis Endomiocárdica/fisiopatología , Resultado Fatal , Humanos , Masculino , Insuficiencia Multiorgánica/etiología , Valor Predictivo de las Pruebas , Resultado del TratamientoRESUMEN
In the study, we used functional magnetic resonance imaging associated with behavioral assessment to observe the effects of venlafaxine on the modulation of human motor cortex activation and to provide preliminary data for further assessing its influence on motor functional reorganization after stroke injury. In a randomized, double-blind, crossover study, 8 right-handed subjects received 75 mg of either venlafaxine or a placebo daily over a period of 7 days separated by 3 washout days. The volunteers were asked to execute motor tasks, which included the dynamometer and finger-tapping test. In addition, laboratory tests and functional magnetic resonance imaging examination, before the start of the experiment and after administration of placebo and venlafaxine, were performed. It was shown that the finger-tapping rate of each hand in the venlafaxine stage was significantly improved compared with that observed in the placebo stage (n = 8, F left hand = 57.69, F right hand = 184.48, P < 0.001). The changes in the recorded grip strengths of both hands were not significant between the stages (n = 8, F = 2.63, P > 0.05). In the venlafaxine stage, the activations of the contralateral primary sensorimotor cortex, contralateral premotor cortex, and contralateral supplementary motor area were enhanced significantly, whereas the activation of the bilateral parietal cortices was decreased when compared with the placebo stage. Meanwhile, the enhancement of contralateral primary sensorimotor cortex activation had a positive correlation with the improvement of the finger-tapping rate. It was concluded that venlafaxine could modulate the cortical excitability and improve finger dexterity and reaction speed, which greatly related to the increase of contralateral motor cortical excitability.
Asunto(s)
Inhibidores de Captación Adrenérgica/farmacología , Antidepresivos/farmacología , Ondas Encefálicas/efectos de los fármacos , Ciclohexanoles/farmacología , Actividad Motora/efectos de los fármacos , Corteza Motora/efectos de los fármacos , Inhibidores Selectivos de la Recaptación de Serotonina/farmacología , Administración Oral , Inhibidores de Captación Adrenérgica/administración & dosificación , Adulto , Antidepresivos/administración & dosificación , Mapeo Encefálico/métodos , China , Estudios Cruzados , Ciclohexanoles/administración & dosificación , Método Doble Ciego , Esquema de Medicación , Lateralidad Funcional , Fuerza de la Mano , Voluntarios Sanos , Humanos , Imagen por Resonancia Magnética , Masculino , Corteza Motora/fisiología , Proyectos Piloto , Tiempo de Reacción/efectos de los fármacos , Inhibidores Selectivos de la Recaptación de Serotonina/administración & dosificación , Factores de Tiempo , Clorhidrato de VenlafaxinaRESUMEN
OBJECTIVE: Chronic inflammatory demyelinating polyneuropathy (CIDP) is an autoimmune disorder of the peripheral nerves with an incompletely understood underlying pathophysiology. This investigation focused on defining B and T cell frequencies, T cell functional capacity and innate immune system analysis in patients with CIDP. METHODS: By using multi-parameter flow cytometry, we examined the phenotype and function of PBMCs in 25 CIDP patients who were relatively clinically stable on treatment who met EFNS/PNS criteria, 21 patients with genetically confirmed hereditary neuropathy and 25 healthy controls. We also evaluated the regulatory T cell (Treg) inhibitory capacity by co-culturing Treg and effector T cells. RESULTS: Proinflammatory CD4 T cells, especially type 1 helper T cell (Th1) and CD8 T cells in patients with CIDP were found to have an enhanced capacity to produce inflammatory cytokines. There was no difference in frequency of Th17 regulatory cells in CIDP patients versus healthy controls, however, Treg function was impaired in CIDP patients. There was no remarkable difference in innate immune system measures. Within B cell subsets, transitional cell frequency was decreased in CIDP patients. INTERPRETATION: Patients with CIDP clinically stable on treatment continued to show evidence of a proinflammatory state with impaired Treg function. This potentially implies an inadequate suppression of ongoing inflammation not addressed by standard of care therapies as well as persistent activity of disease while on treatment. Targeting T cells, especially inhibiting Th1 and polyfunctional CD8 T cells or improving Treg cell function could be potential targets for future therapeutic research.
Asunto(s)
Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante , Humanos , Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante/inmunología , Femenino , Masculino , Persona de Mediana Edad , Adulto , Anciano , Citometría de Flujo , Citocinas/metabolismo , Citocinas/inmunología , Linfocitos T Reguladores/inmunologíaRESUMEN
[This corrects the article DOI: 10.3389/fneur.2022.961628.].
RESUMEN
High impurity concentration of biogas limits its wide commercial utilization. Therefore, the integration of two-stage anaerobic digestion process with in situ biogas upgrading technologies is reviewed, with emphasis on their principles, main influencing factors, research success, and technical challenges. The crucial factors that influence these technologies are pH, alkalinity, and hydrogenotrophic methanogenesis. Hence, pH fluctuation and low gas-liquid mass transfer of H2 are some major technical challenges limiting the full-scale application of in situ upgrading techniques. Two-stage anaerobic digestion integration with various in situ upgrading techniques to form a hybrid system is proposed to overcome the constraints and systematically guide future research design and advance the development and commercialization of these techniques. This review intends to provide the current state of in situ biogas upgrading technologies and identify knowledge gaps that warrant further investigation to advance their development and practical implementation.
Asunto(s)
Biocombustibles , Reactores Biológicos , Anaerobiosis , Metano , Tecnología , Dióxido de Carbono , HidrógenoRESUMEN
Palmd-deficient mice of advanced age manifest increased aortic valve peak velocity, thickened aortic valve leaflets, and excessive extracellular matrix deposition, which are key features of calcific aortic valve disease. PALMD is predominantly expressed in endothelial cells of aortic valves, and PALMD-silenced valvular endothelial cells are prone to oscillatory shear stress-induced endothelial-to-mesenchymal transition. Mechanistically, PALMD is associated with TNFAIP3 interaction protein 1, a binding protein of TNFAIP3 and IKBKG in NF-κB signaling. Loss of PALMD impairs TNFAIP3-dependent deubiquitinating activity and promotes the ubiquitination of IKBKG and subsequent NF-κB activation. Adeno-associated virus-mediated PALMD overexpression ameliorates aortic valvular remodeling in mice with calcific aortic valve disease, indicating protection.
RESUMEN
Py-GC/MS and thermogravimetric analysis were carried out to systematically explore product selectivity and kinetics of poplar sawdust catalytic pyrolysis over bi-metallic Fe-Ni/ZSM-5. The results showed that the Fe-Ni/ZSM-5 exhibited an additive effect on the production of monocyclic aromatic hydrocarbons compared to mono-metallic catalysts (Fe/ZSM-5 or Ni/ZSM-5). Fe-Ni/ZSM-5 further increased the yield of toluene (17.28 mg g-1), which was 41.4% and 80.9% higher than Fe/ZSM-5 and Ni/ZSM-5, respectively. According to the kinetic analysis, the average activation energy obtained from catalytic pyrolysis with Fe-Ni/ZSM-5 using the methods of Friedman, Starink, Flynn-Wall-Ozawa, and Kissinger-Akahira-Sunose was 156.19, 152.39, 154.30, and 152.11 kJ mol-1, respectively. Fe-Ni/ZSM-5 addition lowered the activation energy compared to non-catalytic pyrolysis at the conversion rate of 0.15-0.75. The overall catalytic pyrolysis process of poplar sawdust follows the diffusion and nucleation models. The thermodynamic parameters (enthalpy and entropy) showed positive and negative values, respectively, indicating non-spontaneous reactions during the catalytic pyrolysis process.
Asunto(s)
Níquel , Pirólisis , Biomasa , Catálisis , Hierro , Cinética , TermogravimetríaRESUMEN
We previously found that leflunomide combined with low-dose prednisone rapidly improved the clinical symptoms of myasthenia gravis (MG), but we had not investigated the mechanism of this phenomenon. This study documents the effect of leflunomide combined with low-dose prednisone on pro-inflammatory T cells in MG patients. We compared 32 treated MG patients with 18 controls. We collected peripheral blood before treatment and 4, 8, and 12 weeks after treatment. We extracted peripheral blood mononuclear cells (PBMCs) and stimulated them with phorbol 12-myristate 13-acetate (PMA) + ionomycin and quantified IFN-γ, IL-4, IL-17, and IL-9 secretion through ELISA. We quantified T helper (Th) cells Th1 (CD3+CD4+IFN-γ+), Th2 (CD3+CD4+IL-4+), Th17 (CD3+CD4+IL-17A+) and Th9 (CD3+CD4+IL-9+) among PBMCs. The treatment significantly reduced IL-17 and IL-9 secretion in peripheral blood but did not affect IFN-γ levels. Significant decreases in IL-17 and IL-9 appeared at week 12, and the trend of change was similar to that of the MG composite score. Flow cytometry indicated that leflunomide combined with low-dose prednisone significantly reduced the frequency of Th1 and Th17 cells. These findings demonstrate the potential of this treatment as an alternative immunosuppressive therapy for MG.
RESUMEN
Background: There are different opinions on haemoglobin A1c (HbA1c) in predicting cardiovascular events after percutaneous coronary intervention (PCI). Some factors may affect the ability of HbA1c to predict cardiovascular events, resulting in this inconsistency. Inflammation is a direct and whole-process participant in atherosclerosis. However, no one has studied the effect of inflammation on the correlation between HbA1c and cardiovascular events. Therefore, we aimed to test the hypothesis that high-sensitivity C-reactive protein (hsCRP) modulates HbA1c-related cardiovascular events in patients with the acute coronary syndrome (ACS) undergoing PCI. Methods: This was a retrospective cohort study. We enrolled patients with ACS who were hospitalized for PCI and followed up for 24 months. The primary outcome was the composite of major adverse cardiovascular and cerebrovascular events (MACCEs), including all-cause death, nonfatal myocardial infarction, nonfatal stroke, and unplanned repeat revascularization. We stratified the overall population by HbA1c tertiles and hsCRP median. The relationship between HbA1c, hsCRP, and cardiovascular events was analysed by the Cox proportional hazard regression model. Results: A total of 2,023 patients were enrolled in this study (age: 59.7±10.03 years old, 78.1% male patients). After the 24-month follow-up, 152 (7.51%) events occurred. Patients with hsCRP >1.21 mg/L had an increased cardiovascular risk compared with patients with hsCRP ≤1.21 mg/L [hazard ratio (HR) 1.58, 95% confidence interval (CI): 1.12-2.24, P=0.010]. We did not observe a significant correlation between HbA1c and cardiovascular events. Furthermore, we stratified patients by hsCRP ≤1.21 or >1.21 mg/L and found that the correlation between HbA1c and cardiovascular events was only significant in patients with hsCRP ≤1.21 mg/L (tertile 2 vs. tertile 1: HR 1.76, 95% CI: 0.79-3.90, P=0.165, tertile 3 vs. tertile 1: HR 3.03, 95% CI: 1.50-6.12, P=0.002; P=0.008 for trend) but not in patients with hsCRP >1.21 mg/L. Conclusions: This study showed that hsCRP may affect the relationship between HbA1c and the risk of cardiovascular events in patients with ACS after PCI. This finding suggests that the risk of cardiovascular events may be underestimated when only HbA1c is used as a predictor of cardiovascular risk. HbA1c has a better predictive value in the absence or low levels of inflammation states represented by hsCRP as a predictor of cardiovascular events.
RESUMEN
Background: In percutaneous coronary intervention (PCI) era, more clinically valuable risk factors are still needed to determine the occurrence of cardiac rupture (CR). Therefore, we aimed to provide evidence for the early identification of CR in ST-segment elevation myocardial infarction (STEMI). Methods: A total of 22,016 consecutive patients with STEMI admitted to Cangzhou Central Hospital and Tianjin Chest Hospital from January 2013 to July 2021 were retrospectively included, among which 195 patients with CR were included as CR group. From the rest 21,820 STEMI patients without CR, 390 patients at a ratio of 1:2 were included as the control group. A total of 66 patients accepted PCI in the CR group, and 132 patients who accepted PCI in the control group at a ratio of 1:2 were included. The status of first medical contact, laboratory examinations, and PCI characteristics were recorded. Multivariate logistic regression analysis was used to investigate the risk factors related to CR. Results: There was a higher proportion of patients with myocardial infarction (MI) in the high lateral wall in the CR group (23.6% vs. 8.2%, P<0.001). The proportion of single lesions was lower in the CR group (24.2% vs. 45.5%, P=0.004). Female (OR =2.318, 95% CI: 1.431-3.754, P=0.001), age (OR =1.066, 95% CI: 1.041-1.093, P<0.001), smoking (OR =1.750, 95% CI: 1.086-2.820, P=0.022), total chest pain time (OR =1.017, 95% CI: 1.000-1.035, P=0.049), recurrent acute chest pain (OR =2.750, 95% CI: 1.535-4.927, P=0.001), acute myocardial infarction (AMI) in the high lateral wall indicated by ECG (OR =5.527, 95% CI: 2.798-10.918, P<0.001), acute heart failure (OR =3.585, 95% CI: 2.074-6.195, P<0.001), and NT-proBNP level (OR =1.000, 95% CI: 1.000-1.000, P=0.023) were risk factors for CR in all patients. In patients who accepted PCI, single lesion (OR =0.421, 95% CI: 0.204-0.867, P=0.019), preoperative thrombolysis in myocardial infarction (TIMI) grade (OR =0.358, 95% CI: 0.169-0.760, P=0.007), and postoperative TIMI grade (OR =0.222, 95% CI: 0.090-0.546, P=0.001) were risk factors for CR. Conclusions: Non-single lesions and preoperative and postoperative TIMI grades were risk factors for CR in patients who accepted PCI. In addition to previously reported indicators, we found that AMI in the high lateral wall maybe helpful in early and accurate identification and prevention of possible CR.