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1.
Mol Ther ; 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38879754

RESUMO

Despite the remarkable success of chimeric antigen receptor (CAR) T therapy in hematological malignancies, its efficacy in solid tumors remains limited. Cytokine-engineered CAR T cells offer a promising avenue, yet their clinical translation is hindered by the risks associated with constitutive cytokine expression. In this proof-of-concept study, we leverage the endogenous interferon (IFN)-γ promoter for transgenic interleukin (IL)-15 expression. We demonstrate that IFN-γ expression is tightly regulated by T cell receptor signaling. By introducing an internal ribosome entry site IL15 into the 3' UTR of the IFN-γ gene via homology directed repair-mediated knock-in, we confirm that IL-15 expression can co-express with IFN-γ in an antigen stimulation-dependent manner. Importantly, the insertion of transgenes does not compromise endogenous IFN-γ expression. In vitro and in vivo data demonstrate that IL-15 driven by the IFN-γ promoter dramatically improves CAR T cells' antitumor activity, suggesting the effectiveness of IL-15 expression. Last, as a part of our efforts toward clinical translation, we have developed an innovative two-gene knock-in approach. This approach enables the simultaneous integration of CAR and IL-15 genes into TRAC and IFN-γ gene loci using a single AAV vector. CAR T cells engineered to express IL-15 using this approach demonstrate enhanced antitumor efficacy. Overall, our study underscores the feasibility of utilizing endogenous promoters for transgenic cytokines expression in CAR T cells.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38641315

RESUMO

OBJECTIVE: This multicentre study aimed to assess the early and midterm outcomes of physician modified fenestrated endografts (PMEGs) for endovascular aortic arch repair in zone 0. METHODS: Between 2018 and 2022, a retrospective study was conducted in three centres of consecutive patients undergoing endovascular aortic arch repair in zone 0 with PMEGs. Endpoints included technical success, 30 day mortality rate, major adverse events, secondary interventions, stent stability, target vessel patency, and overall survival. RESULTS: A total of 54 patients (mean age 63 years; 45 males) with aortic arch pathology were included, comprising aortic dissections (n = 32; 59%) and aortic arch aneurysms (n = 22; 41%). Technical success was 98%. One patient died from stroke within 30 days. Major adverse events included stroke (n = 4; 7%), retrograde type A dissection (RTAD) (n = 3; 6%), and acute kidney injury (n = 2; 4%). During a median follow up of 12 months, there were two deaths (4%) of unknown cause at one month and 1.5 months, and no aortic related death. Type Ia, type Ic, and type IIIc endoleaks were observed in two (4%), three (6%), and two (4%) patients, respectively. No vessel stenosis was observed. Re-intervention was required in 10 patients (19%). Estimates of overall survival, freedom from secondary intervention, and freedom from target vessel instability at one year were 94.2% (standard error [SE] 3.3%), 81.8% (SE 6.0%), and 92.0% (SE 4.5%), respectively. CONCLUSION: This study has demonstrated the efficacy of PMEGs for zone 0 endovascular aortic arch repair, with acceptable technical success and mortality rates. Stroke, RTAD, and re-intervention rates remain a concern for endovascular therapy. A larger population and long term outcomes are required to assess the safety and durability of this technique as a beneficial choice for endovascular aortic arch repair in specialised centres.

3.
Am J Otolaryngol ; 45(5): 104358, 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38754262

RESUMO

OBJECTIVE: This case series study investigated the outcomes of an innovative approach, ansa cervicalis nerve (ACN)-to-recurrent laryngeal nerve (RLN) low-tension anastomosis. METHODS: Patients who received laryngeal nerve anastomosis between May 2015 and September 2021 at the facility were enrolled. The inclusion criteria were patients with RLN dissection and anastomosis immediately during thyroid surgery. Exclusion criteria were cases with anastomosis other than cervical loop-RLN anastomosis or pronunciation recovery time > 6 months. Patients admitted before January 2020 were assigned to group A which underwent the conventional tension-free anastomosis, and patients admitted after January 2020 were group B and underwent the innovative low-tension anastomosis (Dong's method). RESULTS: A total of 13 patients were included, 11 patients received unilateral surgery, and 2 underwent bilateral surgery. For patients who underwent unilateral anastomosis, group B had a significantly higher percentage of normal pronunciation via GRBAS scale (83.3 % vs. 0 %, p = 0.015) and voice handicap index (66.7 % vs. 0 %, p = 0.002), and shorter recovery time in pronunciation (median: 1-day vs. 4 months, p = 0.001) than those in group A after surgery. CONCLUSIONS: ACNs-to-RLN low-tension anastomosis with a laryngeal segment ≤1 cm (Dong's method) significantly improves postoperative pronunciation and recovery time. The results provide clinicians with a new strategy for ACN -to-RLN anastomosis during thyroid surgery.

4.
J Endovasc Ther ; : 15266028231207023, 2023 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-37902431

RESUMO

OBJECTIVE: This study aimed to evaluate the outcomes of physician-modified endografts (PMEGs) for the treatment of thoracic aortic pathologies involving the aortic arch. METHODS: A retrospective single-center study was performed on consecutive patients with thoracic aortic pathologies treated by PMEGs between February 2018 and May 2022. Data on baseline characteristics, operative procedure, and follow-up information were collected. The endpoints included technical success, complications, mortality, overall survival, re-intervention, and target vessel instability. RESULTS: This study comprised 173 patients (mean age=58±13, range=28-83, 148 men) with thoracic aortic pathologies, including 44 thoracic aortic aneurysms, 113 aortic dissections (9 type A, 4 residual type A, 75 type B, 32 non-A non-B), 3 aortic intramural hematomas, and 13 penetrating aortic ulcers. Thirty-five of the patients had PMEGs with 3 fenestrations, 32 had 2 fenestrations, and 106 had 1 single fenestration. Technical success was 98% (170/173), and the 30-day mortality was 2% (3/173). Perioperative complications included stroke (n=3, 2%), retrograde type A dissection (RTAD; n=3, 2%) and renal injury (n=3, 2%). Seven deaths (4%) were noted during a median follow-up of 11 (range=1-52) months. Eleven cases of re-intervention were stent-related. There were 5 type Ia endoleaks (3%), 2 type III endoleaks (1%) from the innominate artery (IA), and 3 type Ic endoleaks (2%) from the left subclavian arteries. One case of IA stent-graft (SG) stenosis was noted because of mural thrombus. Estimate rates of overall survival, freedom from secondary intervention, and freedom from target vessel instability at 2 years were 93.4% (95% confidence interval [CI]=88.7%-98.1%), 80.7% (95% CI=73.3%-88.1%), and 89.0% (95% CI=80.4%-97.6%), respectively. CONCLUSIONS: Physician-modified endografts showed promising immediate therapeutic results in the treatment of thoracic aortic pathologies involving the aortic arch. Our study demonstrates that the technique is feasible and produces acceptable results. Long-term outcomes are required for further refinement of this technical approach to confirm technical success and durability over time as a valuable option for endovascular aortic arch repair in specialized centers. CLINICAL IMPACT: Our short- and mid-term outcomes of physician-modified endografts in 173 patients showed promising results compared to other branched/fenestrated techniques and backed up the endovascular repair of the aortic arch. Meanwhile, the technical expertise pointed out in our manuscript, including preloaded guidewire, diameter-reducing wire and inner mini-cuffs, provided reference and technical guidance for our peers. Most importantly, it demonstrated that the PMEG, as a device whose components were all commercially available, might be a better option for emergency surgery and for centers who had no access to custom-made devices.

5.
Thromb J ; 21(1): 121, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38057889

RESUMO

OBJECTIVE: To first induce chronic deep venous thrombosis in the left iliac veins of canines and porcines and then compare these two models to validate endovascular treatment devices. METHODS: Thrombin and fibrinogen were used to produce a solid thrombus in the left iliac veins of a stenosis model. The researchers used venous angiography and histological staining to investigate the progression of thrombosis. RESULTS: A left iliac vein thrombus was successfully formed in all experimental animals, including six Labrador dogs and three Bama miniature pigs, and there was minimal surgical bleeding. All dogs survived until 90 days, and three pigs died on Days 29, 33, and 58. CONCLUSION: The researchers first established the models and then observed the progression of chronic deep venous thrombosis of the iliac vein in large animals for up to 90 days. Dogs are better suited for chronic deep venous thrombosis models due to their uncomplicated anatomy, excellent obedience, and proneness to physical activity compared with pigs.

6.
Biochem Genet ; 61(2): 521-537, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35984539

RESUMO

Circular RNA_0004712 (circ_0004712) is reported to be up-regulated in rheumatoid arthritis (RA) patients. Nevertheless, its role and mechanism in RA pathology remain to be clarified. RNA and protein expression was determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot assay. Cell viability, proliferation, apoptosis, migration, and inflammation were assessed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, 5-ethynyl-20-deoxyuridine assay, flow cytometry, scratch test, and enzyme-linked immunosorbent assay. The target correlation between microRNA-633 (miR-633) and circ_0004712 or TNF receptor associated factor 6 (TRAF6) was verified by dual-luciferase reporter assay and RNA immunoprecipitation assay. Circ_0004712 was up-regulated in RA synovial tissues and RA fibroblast-like synoviocytes (RA-FLSs). Circ_0004712 silencing suppressed the viability, proliferation, migration and inflammatory response and facilitated the apoptosis of RA-FLSs. miR-633 was confirmed to be a direct target of circ_0004712, and miR-633 knockdown reversed circ_0004712 silencing-mediated protective effects on the dysfunction and inflammation of RA-FLSs. TRAF6 was a direct target of miR-633, and miR-633 overexpression suppressed the aggressive changes of RA-FLSs by down-regulating TRAF6. Circ_0004712 could up-regulate TRAF6 expression by sponging miR-633 in RA-FLSs. Circ_0004712 interference inactivated nuclear factor (NF)-κB signaling by targeting miR-633/TRAF6 axis. Circ_0004712 silencing inhibited the aggressive changes of RA-FLSs by targeting miR-633/TRAF6 axis and NF-κB signaling, which provided new targets for RA therapy.


Assuntos
Artrite Reumatoide , MicroRNAs , Sinoviócitos , Humanos , Sinoviócitos/metabolismo , Sinoviócitos/patologia , Fator 6 Associado a Receptor de TNF/genética , Fator 6 Associado a Receptor de TNF/metabolismo , Proliferação de Células/genética , Artrite Reumatoide/genética , Artrite Reumatoide/metabolismo , Inflamação/genética , NF-kappa B/metabolismo , Fibroblastos/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Apoptose/genética , Células Cultivadas
7.
Int J Mol Sci ; 24(22)2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-38003630

RESUMO

GNAQ, a member of the alpha subunit encoding the q-like G protein, is a critical gene in cell signaling, and multiple studies have shown that upregulation of GNAQ gene expression ultimately inhibits the proliferation of gonadotropin-releasing hormone (GnRH) neurons and GnRH secretion, and ultimately affects mammalian reproduction. Photoperiod is a key inducer which plays an important role in gene expression regulation by affecting epigenetic modification. However, fewer studies have confirmed how photoperiod induces epigenetic modifications of the GNAQ gene. In this study, we examined the expression and epigenetic changes of GNAQ in the hypothalamus in ovariectomized and estradiol-treated (OVX+E2) sheep under three photoperiod treatments (short photoperiod treatment for 42 days, SP42; long photoperiod treatment for 42 days, LP42; 42 days of short photoperiod followed by 42 days of long photoperiod, SP-LP42). The results showed that the expression of GNAQ was significantly higher in SP-LP42 than in SP42 and LP42 (p < 0.05). Whole genome methylation sequencing (WGBS) results showed that there are multiple differentially methylated regions (DMRs) and loci between different groups of GNAQ. Among them, the DNA methylation level of DMRs at the CpG1 locus in SP42 was significantly higher than that of SP-LP42 (p < 0.01). Subsequently, we confirmed that the core promoter region of the GNAQ gene was located with 1100 to 1500 bp upstream, and the DNA methylation level of all eight CpG sites in SP42 was significantly higher than those in LP42 (p < 0.01), and significantly higher than those in SP-LP42 (p < 0.01), except site 2 and site 4 in the first sequencing fragment (p < 0.05) in the core promoter region. The expression of acetylated GNAQ histone H3 was significantly higher than that of the control group under three different photoperiods (p < 0.01); the acetylation level of sheep hypothalamic GNAQ genomic protein H3 was significantly lower under SP42 than under SP-LP42 (p < 0.05). This suggests that acetylated histone H3 binds to the core promoter region of the GNAQ gene, implying that GNAQ is epigenetically regulated by photoperiod through histone acetylation. In summary, the results suggest that photoperiod can induce DNA methylation in the core promoter region and histone acetylation in the promoter region of the GNAQ gene, and hypothesize that the two may be key factors in regulating the differential expression of GNAQ under different photoperiods, thus regulating the hypothalamus-pituitary-gonadal axis (HPGA) through the seasonal estrus in sheep. The results of this study will provide some new information to understand the function of epigenetic modifications in reproduction in sheep.


Assuntos
Epigênese Genética , Fotoperíodo , Animais , Feminino , Hormônio Liberador de Gonadotropina/metabolismo , Histonas/genética , Histonas/metabolismo , Hipotálamo/metabolismo , Mamíferos/metabolismo , Ovinos/genética , Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP
8.
Anim Biotechnol ; : 1-6, 2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36332162

RESUMO

The p110δ isoform of the PI3K catalytic subunit (encoded by the PIK3CD gene) is a key component of the PI3K pathway for follicle growth in mammalian ovarian granulosa cells. Nevertheless, little is known about the association of its polymorphisms with ovine litter size. In this study, the distribution of different genotypes of two SNPs in the PIK3CD gene was calculated in more than forty sheep breeds, and the associations between SNPs and litter size in Small Tail Han (STH) sheep were also analyzed. Besides, the mRNA expression of the PIK3CD gene was also detected in some reproduction-related tissues. The results showed that the "A" allele frequency was higher in rs412889931 (g.41926327G > A) in a typical polytocous sheep breed (p < 0.01). The association's analysis showed rs412889931 was correlated with ovine fecundity as assessed by three parity litter sizes (p < 0.05). Finally, we found the expression of PIK3CD in the ovary had significant differences in different fecundity sheep breeds, indicating that SNP may regulate the litter size by influencing the PIK3CD gene expression. The present results demonstrated that rs412889931 could be used in the marker-assisted selection of the litter size in sheep breeding.

9.
J Endovasc Ther ; 27(5): 749-756, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32580618

RESUMO

Purpose: To evaluate the immediate postoperative and midterm outcomes of complex thoracoabdominal aortic aneurysm (TAAA) treatment with fenestrated/branched physician-modified endovascular grafts (PMEGs) or open debranching of the visceral aorta with bypass graft revascularization plus endovascular aneurysm exclusion (hybrid repair). Materials and Methods: A retrospective analysis was conducted of 88 patients (mean age 70.0±10.6 years; 73 men) with complex TAAAs who underwent treatment with PMEGs (60, 68%) or a hybrid technique (28, 32%) between 2016 and 2019. The mean aneurysm diameter was 64.5±11.7 mm, and 37 patients (42%) were symptomatic. The Zenith TX2 and Ankura were the main stent-grafts used in the PMEG group. The hybrid technique involved visceral debranching with extra-anatomical bypass graft revascularization and subsequent stent-graft deployment (1- or 2-stage procedure). Results: In the PMEG group, 35 patients received modified stent-grafts with 4 fenestrations, 8 patients had 4 branches per device, and 17 patients had combinations (50 fenestrations and 18 branches) that successfully revascularized 228 of the 240 targets (95%). In the 28 hybrid cases, all 110 target vessels were successfully revascularized with bypass grafts. The overall 30-day mortality was 3.4% (2 PMEG and 1 hybrid), and the early rate of target vessel stenosis/occlusion was 3.3% (5 in PMEG group and 6 in the hybrid repair group). The 30-day morbidity was mainly attributed to pulmonary complications (15%), lower limb ischemia (8%), or spinal cord ischemia with paraplegia (6%). Eleven patients (13%) had deteriorated renal function with a >30% decrease in the glomerular filtration rate. The mean follow-up was 22.3±4.9 months, and mortality was 4.5% (3.3% in the PMEG group vs 7.1% in the hybrid repair group). Conclusion: PMEGs and hybrid techniques seem to be feasible treatment options for aortic aneurysms necessitating visceral vessel revascularization. PMEGs may have a lower morbidity than the hybrid technique, which nonetheless remains an important option available for complex aortic aneurysms.


Assuntos
Aneurisma da Aorta Torácica/cirurgia , Implante de Prótese Vascular/instrumentação , Prótese Vascular , Procedimentos Endovasculares/instrumentação , Desenho de Prótese , Stents , Idoso , Idoso de 80 Anos ou mais , Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/mortalidade , Aneurisma da Aorta Torácica/fisiopatologia , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/mortalidade , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/mortalidade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
10.
Phys Chem Chem Phys ; 22(14): 7374-7380, 2020 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-32211646

RESUMO

Copper sulfides have attracted great attention recently in the thermoelectric community due to the liquid-like behavior of Cu ions. Among the numerous copper sulfides, digenite Cu1.80S has a poorer thermoelectric performance but better stability than the state-of-the-art binary copper sulfide Cu1.97S. In this study, good stability and high thermoelectric performance were simultaneously obtained in Fe-doped Cu1.80S. Because Fe ions will not form a concentration gradient under an external field to change the critical voltage, Fe-doped Cu1.80S samples inherit the good stability of the pristine Cu1.80S. The critical voltage for Cu1.80Fe0.064S is 0.16 V at 750 K, which has been the largest value reported so far. Likewise, the Fe dopants can significantly improve the thermoelectric performance by suppressing the too high electrical conductivity of Cu1.80S. The peak dimensionless figure of merit (zT) for Cu1.80Fe0.064S is around 0.8 at 750 K, about four times that of Cu1.80S. The average zT for Cu1.80Fe0.064S is 0.40 in 300-750 K, which is amongst the highest values in reported thermoelectric sulfides. Combining the good stability and high thermoelectric performance, the present Cu1.80Fe0.064S has great potential to be used in the application of waste heat harvesting in the middle temperature range.

11.
Appl Opt ; 59(7): 2065-2071, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32225728

RESUMO

Pyramidal structures, including upright pyramids and inverted pyramids (IPs), are commonly used as light-trapping structures for silicon solar cells and silicon photodetectors. In this paper, the possible ray propagation paths in a pyramidal structure are analyzed by establishing a mathematical model in which up to seven ray paths may exist either in a regular or random pyramidal structure. To reduce the reflectivity, the proportion of the quadruple bounce should be increased because of its lower reflectivity. Therefore, a chain IP structure with a quadruple bounce proportion of 10.33% is proposed, of which the overlap value $\Delta x/w$Δx/w is 0.4. According to theoretical ray-tracing calculations, the weighted average reflectivity is reduced by 0.75% compared to that of a random IP structure. Experimentally, chain IP structures are fabricated from the surface line damage produced by the diamond wire sawing of a silicon wafer as a mask, and the reflectivity of the structures is 0.80% lower than that of a random IP structure. The theoretical analysis and experimental results both show that the chain IP structure has better optical properties than the random IP structure, indicating promising prospects for the abovementioned applications.

12.
J Stroke Cerebrovasc Dis ; 29(11): 105221, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33066883

RESUMO

INTRODUCTION: Cerebral small-vessel disease (CSVD) is an extensive cerebrovascular disease associated with many poor outcomes. Previous studies have shown that brachial-ankle pulse wave velocity (baPWV) is related to various neuroimaging signatures, but its association with the total CSVD burden remains unknown. We aimed to explore whether baPWV is related to the total CSVD score and to establish a cutoff for detecting the presence and severity of CSVD, which may guide clinical preventive measures. METHODS: We retrospectively selected 684 neurologically healthy participants to explore correlations between baPWV and the total CSVD score and each of its components (lacunes, white matter hyperintensity (WMH), perivascular space (PVS), and cerebral microbleeds (CMBs)). Subsequently, we established two receiver operating characteristic (ROC) curves to study the effectiveness of baPWV in predicting CSVD (scores 1-4) and severe CSVD (scores 3-4). RESULTS: The median baPWV was 13.16 m/s, which increased significantly with increasing scores (0-4). BaPWV was significantly higher among persons with each component of the total CSVD score than among those without any components. Multivariable ordinal logistic regression analyses showed that a one-unit (m/s) change in baPWV significantly increased the total CSVD score by 0.012. The optimal baPWV cutoffs for detecting CSVD and severe CSVD were 13.12 m/s and 15.63 m/s, respectively. CONCLUSIONS: BaPWV was positively correlated with the total CSVD score, suggesting that baPWV measurement is a useful method for early diagnosis of CSVD, which may contribute to preventing and controlling CSVD progression in the general population of China.


Assuntos
Índice Tornozelo-Braço , Doenças de Pequenos Vasos Cerebrais/diagnóstico , Análise de Onda de Pulso , Rigidez Vascular , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Assintomáticas , Doenças de Pequenos Vasos Cerebrais/epidemiologia , Doenças de Pequenos Vasos Cerebrais/fisiopatologia , China/epidemiologia , Diagnóstico Precoce , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prevalência , Estudos Retrospectivos , Índice de Gravidade de Doença
13.
J Cell Mol Med ; 23(12): 8493-8504, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31633295

RESUMO

MicroRNAs (MiRNAs, MiRs) represent a class of conserved small non-coding RNAs that affect post-transcriptional gene regulation and play a vital role in angiogenesis, proliferation, apoptosis, migration and invasion. They are essential for a wide range of physiological and pathological processes, especially for vascular diseases. However, data concerning miRNAs in endothelial progenitor cells (EPCs) and deep vein thrombosis (DVT) remain incomplete. We explored miRNAs that modulate angiogenesis in EPCs and thrombolysis, and analysed their underlying mechanisms using a DVT model, dual-luciferase reporter assay, qRT-PCR, Western blot, immunofluorescence staining, flow cytometry analysis, CCK-8 assay, angiogenesis assay, wound healing and Transwell assay. We found that miR-205 enhanced the homing ability of EPCs to DVT sites and promoted thrombosis resolution and recanalization, which significantly reduced venous thrombus. Additionally, we demonstrated that miR-205 overexpression significantly enhanced angiogenesis in vivo and in vitro, migration, invasion, F-actin filaments and proliferation in EPCs, and inhibited cell apoptosis. Conversely, down-regulation of miR-205 played the opposite role in EPCs. Importantly, this study demonstrated that miR-205 directly targeted PTEN to modulate the Akt/autophagy pathway and MMP2 expression, subsequently playing a key role in EPC function and DVT recanalization and resolution. These results elucidated the pro-angiogenesis effects of miR-205 in EPCs and established it as a potential target for DVT treatment.


Assuntos
Autofagia/genética , Células Progenitoras Endoteliais/metabolismo , Metaloproteinase 2 da Matriz/genética , MicroRNAs/genética , Neovascularização Fisiológica/genética , PTEN Fosfo-Hidrolase/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Trombose Venosa/genética , Animais , Apoptose/genética , Movimento Celular/genética , Células Cultivadas , Regulação da Expressão Gênica , Humanos , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Camundongos Nus , PTEN Fosfo-Hidrolase/metabolismo , Transdução de Sinais/genética , Trombose Venosa/metabolismo
14.
J Transl Med ; 17(1): 270, 2019 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-31416448

RESUMO

BACKGROUND: Deep venous thrombosis (DVT) of lower extremities is a common thrombotic disease, occurring either in isolation or as a complication of other diseases or procedures. MiR-21 is one of important microRNAs which play critical role in various cellular function. This study aim to determine the effect of miR-21 on endothelial progenitor cells (EPCs) and its role in predicting prognosis of DVT. METHODS: EPCs was isolated from DVT models and control subjects. miR-21 expression was confirmed by RT-PCR. Potential target mRNA was predicted by bioinformatics analysis. EPCs biological functions were examined by CCK-8 and tube formation assay. Besides, miR-21 expression was determined in DVT patients to investigate the correlation between miR-21 expression and prognosis of DVT. Cox proportional hazard regression analyses were also performed to reveal the risk factors associated with prognosis. RESULTS: Here, we found miR-21 was downregulated in EPCs of DVT model rats. Increased miR-21 expression promoted proliferation and angiogenesis of EPCs. Moreover, we demonstrated that FASLG was a target of miR-21 and revealed that FASLG knockdown inhibited function of EPCs. Upregulation of miR-21 led to thrombus resolution in a rat model of venous thrombosis. In addition, lower expression level of miR-21 in DVT patients was associated with an increase of recurrent DVT and post thrombotic syndrome (PTS). Furthermore, Cox proportional hazard regression analyses demonstrated miR-21 expression level as an independent predictor of recurrence of DVT. CONCLUSIONS: Our data revealed a role of miR-21 in regulating biological function of EPCs and could be a predictor for recurrent DVT or PTS.


Assuntos
Células Progenitoras Endoteliais/metabolismo , Células Progenitoras Endoteliais/patologia , Proteína Ligante Fas/metabolismo , MicroRNAs/metabolismo , Neovascularização Fisiológica/genética , Trombose Venosa/genética , Adulto , Animais , Sequência de Bases , Sítios de Ligação , Biomarcadores/metabolismo , Proliferação de Células/genética , Feminino , Regulação da Expressão Gênica , Humanos , Masculino , MicroRNAs/genética , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , Ratos Sprague-Dawley , Recidiva
15.
Microvasc Res ; 123: 35-41, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30315850

RESUMO

Venous thromboembolism (VTE), encompassing deep venous thrombosis (DVT) and pulmonary embolism (PE), is the third most common cardiovascular disease. miR-150 is one of important microRNAs which play critical role in various cellular function such as endothelial progenitor cells (EPCs). In this study, we investigate the effect of miR-150 on EPCs function ex vivo and thrombus resolution in vivo. We determined miR-150 expression in EPCs isolated from DVT patients and control subjects by RT-PCR. Potential target of miR-150 was confirmed by bioinformatics analysis and luciferase reporter respectively. The angiogenesis and proliferation were tested by MTT and tube formation assay. A murine model of venous thrombosis was developed as in vivo model. Finally, the effect of miR-150 on EPCs with inferior venous thrombosis were evaluated in vivo. Our data showed that miR-150 was downregulated in EPCs from DVT patients. By using miR-150 agomir and antagomir, we found that miR-150 promoted angiogenesis and proliferation of EPCs. Bioinformatics analysis revealed SRCIN1 as a target of miR-150 and SRCIN1 knockdown inhibited function of EPCs. Forced expression of miR-150 contributed thrombus resolution in a murine model of venous thrombosis. In general, miR-150 was downregulated in EPCs from DVT. Upregulation of miR-150 promoted angiogenesis and proliferation of EPCs by targeting SRCIN1 in vitro and thrombus resolution in vivo.


Assuntos
Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Proliferação de Células , Células Progenitoras Endoteliais/metabolismo , MicroRNAs/metabolismo , Neovascularização Fisiológica , Trombose Venosa/metabolismo , Proteínas Adaptadoras de Transporte Vesicular/genética , Adolescente , Adulto , Animais , Estudos de Casos e Controles , Células Cultivadas , Modelos Animais de Doenças , Células Progenitoras Endoteliais/patologia , Feminino , Regulação da Expressão Gênica , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Ratos Sprague-Dawley , Transdução de Sinais , Trombose Venosa/genética , Trombose Venosa/patologia , Trombose Venosa/fisiopatologia , Adulto Jovem
16.
Phys Chem Chem Phys ; 21(20): 10497-10504, 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31070626

RESUMO

ß-FeSi2, a semiconductor material made of two of the most earth-abundant elements, has important applications in thermoelectrics, photovoltaics and optoelectronics owing to its attractive properties such as suitable band gap and air stability over a wide temperature range. While point defects always play a vital role in semiconductor materials, only sporadic studies have been dedicated to the defects in ß-FeSi2. Here, using first-principles calculations we systematically investigate the intrinsic point defects in ß-FeSi2. Our results reveal that the formation energies of the intrinsic defects in ß-FeSi2 are high enough to prevent them from forming in a significant concentration under thermal equilibrium growth conditions. As a possible kinetic process generating intrinsic defects, we study the α-to-ß phase transition of FeSi2. We find that the phase transition is a slow process occurring on the time scale of an hour. Incomplete phase transition may lead to kinetically formed intrinsic defects. We further calculate the activation energies of the intrinsic defects and show that the experimentally observed conductivity of pure ß-FeSi2 should be a result of unintentional doping. Possible extrinsic impurities that may lead to n-type and p-type conductivity and their activation energies are calculated, which are in good agreement with available experiments. Our results provide guidance for optimizing the doping strategy of ß-FeSi2 for device applications.

17.
Phys Chem Chem Phys ; 21(39): 22159, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31552965

RESUMO

Correction for 'Thermodynamics, kinetics and electronic properties of point defects in ß-FeSi2' by Jun Chai et al., Phys. Chem. Chem. Phys., 2019, 21, 10497-10504.

18.
Med Sci Monit ; 25: 3771-3777, 2019 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-31110168

RESUMO

BACKGROUND Venous thromboembolism (VT) is a leading cause of maternal mortality and morbidity worldwide. Catheter-directed thrombolysis (CDT) is an effective and safe treatment modality for VT patients. However, the long-term outcome of CDT in pregnancy-related venous thrombosis are unclear. The aim of this study was to assess long-term results of pregnancy-related VT patients. MATERIAL AND METHODS We reviewed 41 pregnancy-related deep venous thrombosis (DVT) patients who underwent CDT from February 2008 to May 2015. Clinical data, including demographic variables, disease location, vascular risk factors, treatment regimen, interventional procedure and complications, were collected retrospectively. Clinical and color-duplex ultrasonography were performed to monitor venous patency during follow-up. Post-thrombotic syndrome (PTS) was assessed with the Villalta scale and quality of life (QOL) was evaluated by the VEINES-QOL/Sym questionnaire. RESULTS Twenty-three patients underwent spontaneous abortion or induced abortion within 3 months before DVT, and 18 patients had DVT during the first 3 months after delivery. Technical success was achieved in all patients. Grade III (complete) lysis was obtained in 15 patients and grade II (partial) lysis was obtained in 21 patients. The follow-up period was 3 years. Twenty-eight patients had venous patency at 3-year follow-up; 36.6% of patients developed mild or moderate PTS (Villalta score 5-14) and 4.8% with severe PTS (Villalta score ≥15). VEINES-QOL/Sym scores were 55.24±7.35 and 53.25±6.65, respectively. CONCLUSIONS Catheter-directed thrombolysis is a reliable and safe treatment modality for postnatal or abortion patients with DVT. CDT can reduce the incidence rate of PTS and increase the quality of life.


Assuntos
Terapia Trombolítica/métodos , Trombose Venosa/terapia , Adulto , Anticoagulantes/uso terapêutico , Cateterismo Periférico/métodos , Catéteres , Feminino , Seguimentos , Humanos , Veia Ilíaca/diagnóstico por imagem , Pessoa de Meia-Idade , Flebografia/métodos , Gravidez , Complicações na Gravidez/terapia , Qualidade de Vida , Estudos Retrospectivos , Resultado do Tratamento , Trombose Venosa/diagnóstico
19.
J Ultrasound Med ; 38(10): 2559-2564, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30693547

RESUMO

OBJECTIVES: To compare ultrasound-guided right brachiocephalic vein (BCV) central venous catheter (CVC) placement to right subclavian vein (SCV) CVC insertion in terms of the puncture success rate and complications. METHODS: A retrospective review was performed for all adult patients who received an ultrasound-guided CVC via the right BCV or right SCV access route between January 2016 and March 2018. The puncture success rates and procedure-related complications were analyzed. RESULTS: Data were analyzed from 755 adult patients who underwent 915 CVC insertions. The overall success rate was higher in the BCV group compared to that in the SCV group (98.99% versus 96.87%; P = .019). The first-attempt success rate was higher in the BCV group compared to that in the SCV group (96.64% versus 89.34%; P < .001). Intraoperative complications were observed in 16 cases in the BCV group (2.68%) and in 12 cases in the SCV group (3.76%). The incidence rates of postprocedure complications were 5.20% in the BCV group and 6.58% in the SCV group and included catheter-related infections and thrombosis. CONCLUSIONS: Ultrasound-guided cannulation of the right BCV is an effective and safe method for CVC placement in adult patients and provides an additional option for catheter access.


Assuntos
Veias Braquiocefálicas/diagnóstico por imagem , Cateterismo Venoso Central/métodos , Veia Subclávia/diagnóstico por imagem , Ultrassonografia de Intervenção/métodos , Cateteres Venosos Centrais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
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