RESUMO
BACKGROUND: Cell division control 42 (CDC42) regulates atherosclerosis, blood lipids, and inflammation and thus affects coronary artery disease (CAD), but its utility in drug-coated balloon (DCB)-treated small-vessel CAD (SV-CAD) patients is unclear. This study intended to evaluate the change and prognostic role of CDC42 in SV-CAD patients underwent DCB. METHODS: Serum CDC42 was measured by enzyme-linked immunosorbent assay in 211 SV-CAD patients underwent DCB at baseline, day (D) 1, D3, and D7, as well as in 50 healthy controls (HCs). RESULTS: CDC42 was decreased in SV-CAD patients compared to HCs (P < 0.001), and it was negatively associated with total cholesterol (P = 0.015), low-density lipoprotein cholesterol (P = 0.003), C-reactive protein (P = 0.001), multivessel disease (P = 0.020), and American college of cardiology/American heart association type B2/C lesions (P = 0.039) in SV-CAD patients. Longitudinally, CDC42 decreased from baseline to D1 and then gradually increased to D7 (P < 0.001) in SV-CAD patients after DCB. Interestingly, high CDC42 (cut-off value = 500 pg/mL) at baseline (P = 0.047), D3 (P = 0.046), and D7 (P = 0.008) was associated with a lower accumulating target lesion failure (TLF) rate; high CDC42 at D3 (P = 0.037) and D7 (P = 0.041) was related to a lower accumulating major adverse cardiovascular event (MACE) rate in SV-CAD patients underwent DCB. Importantly, CDC42 at D7 (high vs. low) independently predicted lower accumulating TLF (hazard ratio (HR) = 0.145, P = 0.021) and MACE (HR = 0.295, P = 0.023) risks in SV-CAD patients underwent DCB. CONCLUSIONS: Circulating CDC42 level relates to milder disease conditions and independently estimates lower risks of TLF and MACE in SV-CAD patients underwent DCB, but further validation is still needed.
Assuntos
Doença da Artéria Coronariana , Stents Farmacológicos , Intervenção Coronária Percutânea , Humanos , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/terapia , Doença da Artéria Coronariana/etiologia , Intervenção Coronária Percutânea/efeitos adversos , Resultado do Tratamento , ColesterolRESUMO
Cancer and autism spectrum disorder/developmental delay (ASD/DD) are two common clinical phenotypes in individuals with germline PTEN variants (PTEN hamartoma tumor syndrome, PHTS). Burgeoning studies have shown that genomic and metabolomic factors may act as modifiers of ASD/DD versus cancer in PHTS. Recently, we showed copy number variations to be associated with ASD/DD versus cancer in these PHTS individuals. We also found that mitochondrial complex II variants occurring in 10% of PHTS individuals modify breast cancer risk and thyroid cancer histology. These studies suggest that mitochondrial pathways could act as important factors in PHTS phenotype development. However, the mitochondrial genome (mtDNA) has never been systematically studied in PHTS. We therefore investigated the mtDNA landscape extracted from whole-genome sequencing data from 498 PHTS individuals, including 164 with ASD/DD (PHTS-onlyASD/DD), 184 with cancer (PHTS-onlyCancer), 132 with neither ASD/DD nor cancer (PHTS-neither), and 18 with both ASD/DD and cancer (PHTS-ASDCancer). We demonstrate that PHTS-onlyASD/DD has significantly higher mtDNA copy number than PHTS-onlyCancer group (p = 9.2 × 10-3 in all samples; p = 4.2 × 10-3 in the H haplogroup). PHTS-neither group has significantly higher mtDNA variant burden than PHTS-ASDCancer group (p = 4.6 × 10-2); the PHTS-noCancer group (PHTS-onlyASD/DD and PHTS-neither groups) also shows higher variant burden than the PHTS-Cancer group (PHTS-onlyCancer and PHTS-ASD/Cancer groups; p = 3.3 × 10-2). Our study implicates the mtDNA as a modifier of ASD/DD versus cancer phenotype development in PHTS.
Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Genoma Mitocondrial , Síndrome do Hamartoma Múltiplo , Neoplasias da Glândula Tireoide , Humanos , Síndrome do Hamartoma Múltiplo/genética , Transtorno Autístico/genética , Transtorno do Espectro Autista/genética , Genoma Mitocondrial/genética , Variações do Número de Cópias de DNA/genética , Fenótipo , Neoplasias da Glândula Tireoide/genética , DNA Mitocondrial/genética , PTEN Fosfo-Hidrolase/genéticaRESUMO
OBJECTIVE: To compare the improvement effect between simultaneous electroacupuncture at antagonistic muscle and agonistic muscle and simple electroacupuncture at antagonistic muscle on spasticity degree, upper-extremity motor function and activity of daily living in patients with upper-extremity spasticity after stroke. METHODS: A total of 60 patients with upper-extremity spasticity after stroke were randomized into a comprehensive group (30 cases, 1 case dropped off) and an antagonistic muscle group (30 cases, 2 cases dropped off). In the antagonistic muscle group, acupuncture was applied at Jianyu (LI 15), Binao (LI 14), Zhouliao (LI 12), Shousanli (LI 10), Waiguan (TE 5) and Houxi (SI 3), electric stimulation was attached to Jianyu (LI 15)-Binao (LI 14), Zhouliao (LI 12)-Shousanli (LI 10) and Waiguan (TE 5)-Houxi (SI 3), with discontinuous wave, 15 Hz in frequency. On the basis of the treatment in the antagonistic muscle group, acupuncture was applied at Tianquan (PC 2), Chize (LU 5), Jianshi (PC 5) and Daling (PC 7) in the comprehensive group, electric stimulation was attached to Tianquan (PC 2)-Chize (LU 5) and Jianshi (PC 5)-Daling (PC 7), with continuous wave, 5 Hz in frequency. The treatment was given once a day, 6 days a week for 4 weeks in the two groups. Before and after treatment, the scores of modified Ashworth scale (MAS), Fugl-Meyer assessment upper extremity scale (FMA-UE) and modified Barthel index (MBI) scale were observed in the two groups. RESULTS: Compared before treatment, the MAS scores of elbow flexors and wrist flexors after treatment were decreased (P<0.05), the scores of FMA-UE and MBI scale after treatment were increased in the two groups (P<0.05). The scores of FMA-UE and MBI scale after treatment in the comprehensive group were higher than those in the antagonistic muscle group (P<0.05). CONCLUSION: Simultaneous electroacupuncture at antagonistic muscle and agonistic muscle and simple electroacupuncture at antagonistic muscle can both improve the spasticity degree in patients with upper-extremity spasticity after stroke, however, the former can better restore motor function and improve activity of daily living.
Assuntos
Eletroacupuntura , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Hormônios Esteroides Gonadais , Humanos , Espasticidade Muscular/etiologia , Espasticidade Muscular/terapia , Músculos , Acidente Vascular Cerebral/terapia , Resultado do Tratamento , Extremidade SuperiorRESUMO
The poor conductivity of sulfur, the lithium polysulfide's shuttle effect, and the lithium dendrite problem still impede the practical application of lithium-sulfur (Li-S) batteries. In this work, the ultrathin nickel-doped tungsten sulfide anchored on reduced graphene oxide (Ni-WS2@rGO) is developed as a new modified separator in the Li-S battery. The surface engineering of Ni-WS2@rGO could enhance the cell conductivity and afford abundant chemical anchoring sites for lithium polysulfides (LiPSs) adsorption, which is convinced by the high adsorption energy and the elongate SS bond given using density-functional theory (DFT) calculation. Concurrently, the Ni-WS2@rGO as a modified separator could effectively catalyze the conversion of LiPSs during the charging/discharging process. The Li-S cell with Ni-WS2@rGO modified separator achieves a high initial capacity of 1160.8 mA h g-1 at the current density of 0.2C with a high-sulfur-content cathode up to 80 wt%, and a retained capacity of 450.7 mA h g-1 over 500 cycles at 1C, showing an efficient preventing polysulfides shuttle to the anode while having no influence on Li+ ion transference across the decorating separator. The strategy adopted in this work would afford an effective pathway to construct an advanced functional separator for practical high-energy-density Li-S batteries.
RESUMO
Transition metal oxalates have attracted wide attention due to the characteristics of the conversion reaction as anode materials in lithium-ion batteries (LIBs) and sodium-ion batteries (SIBs), However, there are huge volume expansion and sluggish circulation dynamics during the reversible Li+ and Na+ insertion/extraction process, which would lead to unsatisfactory reversible capacity and stability. In order to solve these problems, a rod-like structure Ni0.5Co0.5C2O4·2H2O is in-situ formed on the reduced graphene oxide layer (Ni0.5Co0.5C2O4·2H2O/rGO) in a glycol-water mixture medium via an interface induced engineering strategy. Benefitting from the synergistic cooperation of nano-diameter rod-like structure and high conductive rGO networks, the experimental results show that the prepared Ni0.5Co0.5C2O4·2H2O/rGO electrode has predominant rate performance and ultra-long cycle stability. For the LIBs, it not only exhibits an ultrahigh reversible capacity (1179.9â¯mAâ¯hâ¯g-1 at 0.5 A g-1 after 300 cycles), but also presents outstanding rate and cycling performance (646.5â¯mAâ¯hâ¯g-1 at 5 A g-1 after 1200 cycles). Besides, the Ni0.5Co0.5C2O4·2H2O/rGO electrode displays remarkable sodium storage capacity of 221.6â¯mAâ¯hâ¯g-1 after 100 cycles at 0.5 A g-1. Further, the extraordinary electrochemical capability of Ni0.5Co0.5C2O4·2H2O/rGO active material is also reflected in two full-cells, assembled using commercial LiCoO2 as cathode for LIBs and commercial Na3V2(PO4)3 as cathode for SIBs, both of which can show wonderful specific capacity and cycling stability. It is found in in-situ Raman experiments that the reversible changes of oxalate peaks are monitored in a charge/discharge process, which is scientific evidence for the transform reaction mechanism of metal oxalates in LIBs. These findings not only provide important ideas for studying the charge/discharge storage mechanism but also give scientific basis for the design of high-performance electrode materials.
RESUMO
Background We sought to determine whether mitochondrial DNA (mtDNA) content can be used as markers for 12 key phenotypes among cardiovascular disease patients, and whether these markers are valid across patients with diverse ancestries. Methods and Results DNA was collected from the peripheral blood of 996 cardiovascular disease patients at the Cleveland Clinic. The mtDNA copy number and DNA-level variation were assessed from whole-genome sequence. Patients were also ascertained retrospectively for histories of 10 clinical events, as well as for maximum stenosis and extent of disease at baseline. Self-reported race and maternal ancestry inferred from mtDNA sequence were recorded. MtDNA copy number and overall mtDNA rare variant load were significantly lower in patients with histories of various adverse clinical events, and mtDNA copy number was inversely correlated with extent of disease. Strong associations were also found between absence of rare variants in the genes MT-ATP6 and MT-COII and patient histories of hyperlipidemia and myocardial infarction, respectively. Importantly, associations were not ancestry dependent. Conclusions This study provides evidence that mtDNA copy number in circulation is associated with a variety of cardiovascular disease patient phenotypes. Results also suggest a protective role for some rare inherited mtDNA variants. Overall, the study supports the potential of mtDNA content and abundance as biomarkers in heart disease, in a manner that is valid across diverse ancestries.
Assuntos
Doenças Cardiovasculares/genética , DNA Mitocondrial/sangue , DNA Mitocondrial/genética , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Estudos ProspectivosRESUMO
To obtain MOFs materials with good electrochemical performance in both lithium-ion batteries (LIBs) and sodium-ion batteries (SIBs), a kind of hollow urchins Co-MOF with doping fluorine (F) was in-situ assembled on reduced graphene oxide (rGO) using a simple solvothermal reaction. According to XRD, XPS and EDS mapping analysis, the molecular structure should be Co2[Fx(OH)1-x]2(C8O4H4) (denoted as F-Co-MOF). When the composite material is used as active material to assemble LIBs, it not only presents the outstanding reversible capacity (1202.0 mA h g-1 at 0.1 A g-1), but also gives the excellent rate performance and cycle performance (771.5 mA h g-1 at 2 A g-1 after 550 repeated cycles). The remarkable lithium storage capacity of F-Co-MOF/rGO is also reflected in the full cell, where it can still maintain a high capacity of 165.2 mA h g-1 after 300 cycles at 0.2 A g-1. It benefits from the synergistic effect of F-Co-MOF and high conductive rGO networks, so that the reversibility of lithium and sodium storage can be improved. This kind of F doped solvothermal synthesis of MOFs is of great significance for the exploration of high performance materials.
RESUMO
Metal oxalate has become a most promising candidate as an anode material for lithium-ion and sodium-ion batteries. However, capacity decrease owing to the volume expansion of the active material during cycling is a problem. Herein, a rod-like CoC2 O4 â 2 H2 O/rGO hybrid is fabricated through a novel multistep solvo/hydrothermal strategy. The structural characteristics of the CoC2 O4 â 2 H2 O microrod wrapped using rGO sheets not only inhibit the volume variation of the hybrid electrode during cycling, but also accelerate the transfer of electrons and ions in the 3 D graphene network, thereby improving the electrochemical properties of CoC2 O4 â 2 H2 O. The CoC2 O4 â 2 H2 O/rGO electrode delivers a specific capacity of 1011.5â mA h g-1 at 0.2â A g-1 after 200 cycles for lithium storage, and a high capacity of 221.1â mA h g-1 at 0.2â A g-1 after 100 cycles for sodium storage. Moreover, the full cell CoC2 O4 â 2 H2 O/rGO//LiCoO2 consisting of the CoC2 O4 â 2 H2 O/rGO anode and LiCoO2 cathode maintains 138.1â mA h g-1 after 200 cycles at 0.2â A g-1 and has superior long-cycle stability. In addition, inâ situ Raman spectroscopy and inâ situ and exâ situ X-ray diffraction techniques provide a unique opportunity to understand fully the reaction mechanism of CoC2 O4 â 2 H2 O/rGO. This work also gives a new perspective and solid research basis for the application of metal oxalate materials in high-performance lithium-ion and sodium-ion batteries.
RESUMO
Vascular calcification is a common problem in the elderly with diabetes, heart failure and end-stage renal disease. The differentiation of vascular smooth muscle cells (VSMCs) into osteoblasts is the main feature, but the exact mechanism remains unclear. It is not clear whether adiponectin (APN) affects osteogenic differentiation of VSMCs. This study aims to explore the effect of APN on vascular calcification by using a cell model induced by beta-glycerophosphate (beta-GP). VSMCs were isolated and treated with beta-GP and APN in this study. The alkaline phosphatase (ALP) activity and expression levels of Runx2, BMP-2, collagen type I and osteocalcin were determined. The expression levels of STAT3 and p-STAT3 in nucleus and cytoplasm of VSMCs were analyzed. The results showed that APN significantly inhibited the expression of ALP, Runx2, BMP-2, collagen I, osteocalcin and the formation of the mineralized matrix in VSMCs induced by beta-GP. APN reduces the osteogenic differentiation of VSMCs induced by beta-GP and down-regulates the expression of the osteogenic transcription factor osterix by inhibiting STATS3 phosphorylation and nuclear transport. APN may be one of the potential candidates for clinical treatment of vascular calcification.
Assuntos
Adiponectina/genética , Osteogênese/genética , Fator de Transcrição STAT3/genética , Calcificação Vascular/genética , Animais , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Glicerofosfatos/farmacologia , Humanos , Janus Quinase 2/antagonistas & inibidores , Janus Quinase 2/genética , Camundongos , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Osteogênese/efeitos dos fármacos , RNA/genética , Fator de Transcrição STAT3/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Fator de Transcrição Sp7/genética , Calcificação Vascular/induzido quimicamente , Calcificação Vascular/patologiaRESUMO
Oxidized low density lipoprotein (ox-LDL) can induce the proliferation and differentiation of endothelial cells, which is one of the important mechanisms of ox-LDL atherosclerosis. Adiponectin is an endogenous bioactive polypeptide secreted by adipocytes, it participates in the metabolism of fat and glucose. It has the effect of reducing blood triglyceride and LDL content. Adiponectin also inhibits the abnormal proliferation and migration of endothelial cells, but its molecular mechanism is unclear. In this study, we used cell model of Ox-LDL-induced human aortic endothelial cells (HAECs) proliferation to analyze the molecular mechanism of APN inhibiting HAECs abnormal proliferation. The results showed that APN could inhibit the cell viability and DNA synthesis of HAECs after Ox-LDL treatment, up-regulate the apoptosis level and reduce the proportion of Sâ¯+â¯G2 phase cells. Further analysis showed that adiponectin could promote the dephosphorylation of Caveolin-1, which could dissociate eNOS and Caveolin-1, promote the phosphorylation of eNOS and enhance the synthesis of NO. NO increased expression levels of cleaved caspase 3 and p21 in the cells and inhibited the abnormal proliferation of HAECs. The regulation of phosphorylation and dephosphorylation of Caveolae-1 plays a key role in this process. Further study of the molecular mechanism of Caveolae-1 in the inhibition of HAECs abnormal proliferation by APN may reveal the potential of APN in the treatment of cardiovascular diseases.
Assuntos
Adiponectina/farmacologia , Proliferação de Células/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Lipoproteínas LDL , Aorta , Caspase 3/metabolismo , Caveolina 1/metabolismo , Linhagem Celular , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Células Endoteliais/metabolismo , Humanos , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Fosforilação/efeitos dos fármacos , Regulação para CimaRESUMO
OBJECTIVE: One aim of this study was to investigate the effects of acupuncture on cerebral function of patients with acute cerebral infarction. Another goal was to evaluate the relationship between acupuncture treatment and motor recovery patients with stroke and to provide a foundation for using acupuncture therapy for such patients. DESIGN: Twenty (20) patients with recent cerebral infarction were divided randomly to an acupuncture group and a control group. The infarction area in each patient was in the basal ganglia or included the basal ganglia with an area size of > 1 cm(2). Serial diffusion tensor imaging (DTI), fluid-attenuated inversion recovery (FLAIR), and T2-weighted imaging (T(2)WI) scans were performed on all patients and the results were evaluated using the National Institute of Health Stroke Scale and the Barthel Index each week. DTI images were postprocessed and analyzed. Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values of abnormal signals on DTI in the infarction areas and cerebral peduncles were calculated for both groups and compared with one another. RESULTS: (1) The ADC value of infarction lesions decreased at stroke onset; then, a significant elevation was observed after the acute stage, and a significant reduction in FA values was observed from stroke onset to the chronic stage. (2) The ADC of the bilateral cerebral peduncle was reduced on the infarction side. (3) There was a significant difference in ADC and FA values between the acupuncture and control groups. The FA value was higher in the acupuncture group than the control group. CONCLUSIONS: ADC and FA values might correlate to patient recovery and reveal the progress of secondary degeneration. Acupuncture treatment is effective for protecting neurons and facilitating recovery.