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1.
Plant J ; 114(4): 895-913, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36987558

RESUMO

5'-3' exoribonucleases (XRNs) play crucial roles in the control of RNA processing, quality, and quantity in eukaryotes. Although genome-wide profiling of RNA decay fragments is now feasible, how XRNs shape the plant mRNA degradome remains elusive. Here, we profiled and analyzed the RNA degradomes of Arabidopsis wild-type and mutant plants with defects in XRN activity. Deficiency of nuclear XRN3 or cytoplasmic XRN4 activity but not nuclear XRN2 activity greatly altered Arabidopsis mRNA decay profiles. Short excised linear introns and cleaved pre-mRNA fragments downstream of polyadenylation sites were polyadenylated and stabilized in the xrn3 mutant, demonstrating the unique function of XRN3 in the removal of cleavage remnants from pre-mRNA processing. Further analysis of stabilized XRN3 substrates confirmed that pre-mRNA 3' end cleavage frequently occurs after adenosine. The most abundant decay intermediates in wild-type plants include not only the primary substrates of XRN4 but also the products of XRN4-mediated cytoplasmic decay. An increase in decay intermediates with 5' ends upstream of a consensus motif in the xrn4 mutant suggests that there is an endonucleolytic cleavage mechanism targeting the 3' untranslated regions of many Arabidopsis mRNAs. However, analysis of decay fragments in the xrn4 mutant indicated that, except for microRNA-directed slicing, endonucleolytic cleavage events in the coding sequence rarely result in major decay intermediates. Together, these findings reveal the major substrates and products of nuclear and cytoplasmic XRNs along Arabidopsis transcripts and provide a basis for precise interpretation of RNA degradome data.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Exorribonucleases/genética , Precursores de RNA , Estabilidade de RNA/genética , Proteínas Nucleares/metabolismo
2.
Exp Brain Res ; 239(1): 1-19, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33170341

RESUMO

Motor learning encompasses a broad set of phenomena that requires a diverse set of experimental paradigms. However, excessive variation in tasks across studies creates fragmentation that can adversely affect the collective advancement of knowledge. Here, we show that motor learning studies tend toward extreme fragmentation in the choice of tasks, with almost no overlap between task paradigms across studies. We argue that this extreme level of task fragmentation poses serious theoretical and methodological barriers to advancing the field. To address these barriers, we propose the need for developing common 'model' task paradigms which could be widely used across labs. Combined with the open sharing of methods and data, we suggest that these model task paradigms could be an important step in increasing the robustness of the motor learning literature and facilitate the cumulative process of science.

3.
Acta Cardiol Sin ; 37(3): 232-238, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33976506

RESUMO

BACKGROUND: The SYNTAX score is an index of coronary severity used to determine the revascularization strategy of a patient. Our previous study confirmed that the SYNTAX score is helpful in predicting major adverse cardiac events in patients with stable coronary artery disease (CAD). However, few studies have comprehensively investigated the predictors for SYNTAX scores in patients with stable CAD, including conventional risk factors, lipid parameters, inflammatory markers and adipokines. METHODS: The coronary severities of 181 revascularization-naïve CAD patients who had received coronary angiograms were coded using SYNTAX scores. Conventional risk factors, inflammatory markers, and adipokines were investigated in order to determine the independent predictors for SYNTAX severity in the patients with stable CAD. RESULTS: The SYNTAX severity score was divided according to the generally accepted criterion (low: ≤ 22, intermediate-high: ≥ 23). In univariate comparisons, the intermediate-high SYNTAX group had a significantly higher low-density lipoprotein cholesterol (LDL-C) level compared to the low SYNTAX score group (p = 0.046). In binary logistic regression, LDL-C, total cholesterol, ratio of total cholesterol/high-density lipoprotein cholesterol (HDL-C) and pre- admission statin use were significant predictors for a higher SYNTAX severity score in the patients with stable CAD. In contrast, circulating adipokines, high-sensitivity C-reactive protein and HDL-C alone were not. CONCLUSIONS: In revascularization-naïve CAD patients, dyslipidemia, including elevated LDL-C, total cholesterol, total cholesterol/HDL-C ratio and pre-index admission statin use, were associated with an intermediate-high SYNTAX severity score.

4.
Acta Cardiol Sin ; 36(5): 428-438, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32952352

RESUMO

BACKGROUND: The use of Complex and High-risk Coronary Interventions (CHIPs) has increased in recent years. Both rotational atherectomy (RA) and hemodynamic support are important parts of CHIPs. OBJECTIVES: This study aimed to retrospectively investigate the procedure results and clinical outcomes of intra-aortic balloon pump (IABP)-assisted RA in the contemporary drug-eluting stent era. METHODS: All consecutive patients who received RA under in-procedure IABP assistance from April 2010 to March 2018 were analyzed retrospectively. RESULTS: A total of 63 patients (77.7 ± 10.1 years, 69.8% male) were recruited, of whom 51 underwent RA with primary IABP assistance and 12 underwent bailout IABP. RA could be completed in 61 (96.8%) of the patients. Overall, vessel perforation, profound in-procedure shock, and ventricular arrhythmia occurred in 1.6%, 4.8% and 3.2% of the patients, respectively. The in-hospital, 30-day and 90-day major adverse cardiac event (MACE) rates were 22.2%, 27.4% and 36.1%, respectively, mostly driven by mortality. The MACE rates were significantly higher in the bail-out group in the hospital (50.0% vs. 15.7%, p = 0.018) at 30 days (58.3% vs. 20.0%, p = 0.013) and 90 days (66.7% vs. 28.6%, p = 0.020). CONCLUSIONS: Bail-out IABP was associated with increased MACEs, implying that the use of IABP should be implemented at the beginning of RA if a complex procedure is anticipated.

5.
J Interv Cardiol ; 2019: 9896267, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31772555

RESUMO

BACKGROUND: To evaluate the acute angiographic and intermediate-term clinical results of patients with non-left main (LM) coronary artery bifurcation disease (CABD) treated with BVS, as compared with those treated with DES, using the jailed semi-inflated balloon technique (JSIBT) for side branch (SB) protection and provisional stenting. METHODS AND RESULTS: Sixty-eight patients with non-LM CABD who had undergone provisional one-stent implantation with SB protection by JSIBT between January 2015 and December 2017 were retrospectively enrolled. Among them, 20 patients received Absorb BVS implantation and 48 patients received DES implantation. Patients in the BVS group were younger and had higher BMI, total cholesterol, low-density lipoprotein cholesterol, and hemoglobin but had lower serum creatinine and lower prevalence of prior PCI and MI. No SB balloon rupture/entrapment occurred in either group. The incidence of SB dissection/occlusion and SB in need of rewiring or stenting was rare in both groups and showed no significant difference between them. Postinterventional TIMI flow significantly increased in both groups. The intermediate-term clinical outcomes were good in terms of incidence of target lesion failure, target lesion revascularization, target vessel revascularization, myocardial infarction, and all-cause death in both groups. CONCLUSION: The use of JSIBT for treating CABD with modern BVS can provide SB protection as similar as those with DES, even with higher incidence of acute SB dissection/occlusion. The immediate angiographic results and acute and intermediate-term clinical outcomes were also similar in both groups. Our study results demonstrate that JSIBT might be a safe and alternative SB protection tool for BVS in patients with complex CABD.


Assuntos
Angioplastia Coronária com Balão , Angiografia Coronária/métodos , Doença da Artéria Coronariana , Vasos Coronários , Complicações Pós-Operatórias , Idoso , Angioplastia Coronária com Balão/efeitos adversos , Angioplastia Coronária com Balão/instrumentação , Angioplastia Coronária com Balão/métodos , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/cirurgia , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/cirurgia , Stents Farmacológicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Processos e Resultados em Cuidados de Saúde/métodos , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Taiwan/epidemiologia , Resultado do Tratamento
6.
BMC Cardiovasc Disord ; 19(1): 208, 2019 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-31477022

RESUMO

BACKGROUND: Percutaneous coronary intervention for coronary artery bifurcation disease (CABD) remains challenging. In patients of CABD with situations that two-stent strategy is needed, the culotte technique is a widely used method and also as the majority at out institution. We sought to take a look of the clinical outcomes of our culotte stenting patients. METHODS: This retrospective study analyzed 238 consecutive CABD patients who underwent culotte two-stent technique at a tertiary medical center between July 2008 and November 2015. RESULTS: Culotte technique was used in 238 lesions in 238 patients. Of these patients, all DES were implanted for culotte two-stent technique. Most of these patients were elderly, male gender, ACS on admission and multiple vessel disease. The bifurcation lesions were mostly located at left coronary artery (51.3%), categorized as true bifurcation lesion (92%) and calculated less than 70 degree of bifurcation angle (74.4%). During a medium 3.27-year follow up, the angle of bifurcation lesion ≥70° and body mass index were positively independent predictors for target lesion failure (TLF), diabetes mellitus was an independent predictor of target vessel revascularization, and statin therapy for hyperlipidemia, hemoglobin and EF were negatively independent factors associated to total mortality. The rates of in-hospital and total mortalities were 4.2 and 17.6%. CONCLUSION: In this cohort of CABD patients with most left main and left anterior descending artery lesions treated by culotte stenting, the procedural success rate was high and the intermediate clinical outcomes were acceptable. (Reviewer #1, Comment #1) Bifurcation angle (≥ 70°) is an inherently independent predictor of TLF and other two-stent strategy replaced needed to be considered in this situation.


Assuntos
Síndrome Coronariana Aguda/terapia , Angioplastia Coronária com Balão/instrumentação , Doença da Artéria Coronariana/terapia , Stents Farmacológicos , Síndrome Coronariana Aguda/diagnóstico por imagem , Síndrome Coronariana Aguda/mortalidade , Idoso , Idoso de 80 Anos ou mais , Angioplastia Coronária com Balão/efeitos adversos , Angioplastia Coronária com Balão/mortalidade , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/mortalidade , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Taiwan , Fatores de Tempo , Resultado do Tratamento
7.
Int J Mol Sci ; 20(2)2019 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-30634691

RESUMO

Continuous passive motion (CPM) is widely used after total knee replacement. In this study, we investigated the effect of CPM combined with cell-based construct-transplantation in osteochondral tissue engineering. We created osteochondral defects (3 mm in diameter and 3 mm in depth) in the medial femoral condyle of 36 knees and randomized them into three groups: ED (empty defect), EPC/PLGA (endothelial progenitor cells (EPCs) seeded in the poly lactic-co-glycolic acid (PLGA) scaffold), or EPC/PLGA/CPM (EPC/PLGA scaffold complemented with CPM starting one day after transplantation). We investigated the effects of CPM and the EPC/PLGA constructs on tissue restoration in weight-bearing sites by histological observation and micro-computed tomography (micro-CT) evaluation 4 and 12 weeks after implantation. After CPM, the EPC/PLGA construct exhibited early osteochondral regeneration and prevention of subchondral bone overgrowth and cartilage degeneration. CPM did not alter the microenvironment created by the construct; it up-regulated the expression of the extracellular matrix components (glycosaminoglycan and collagen), down-regulated bone formation, and induced the biosynthesis of lubricin, which appeared in the EPC/PLGA/CPM group after 12 weeks. CPM can provide promoting signals during osteochondral tissue engineering and achieve a synergistic effect when combined with EPC/PLGA transplantation, so it should be considered a non-invasive treatment to be adopted in clinical practices.


Assuntos
Regeneração Óssea , Condrogênese , Células Progenitoras Endoteliais/citologia , Células Progenitoras Endoteliais/metabolismo , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Engenharia Tecidual , Alicerces Teciduais , Animais , Cartilagem Articular/metabolismo , Cartilagem Articular/patologia , Imuno-Histoquímica , Masculino , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Porosidade , Coelhos , Alicerces Teciduais/química , Microtomografia por Raio-X
8.
Int J Mol Sci ; 20(2)2019 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-30650528

RESUMO

Repairing damaged articular cartilage is challenging due to the limited regenerative capacity of hyaline cartilage. In this study, we fabricated a bilayered poly (lactic-co-glycolic acid) (PLGA) scaffold with small (200⁻300 µm) and large (200⁻500 µm) pores by salt leaching to stimulate chondrocyte differentiation, cartilage formation, and endochondral ossification. The scaffold surface was treated with tyramine to promote scaffold integration into native tissue. Porcine chondrocytes retained a round shape during differentiation when grown on the small pore size scaffold, and had a fibroblast-like morphology during transdifferentiation in the large pore size scaffold after five days of culture. Tyramine-treated scaffolds with mixed pore sizes seeded with chondrocytes were pressed into three-mm porcine osteochondral defects; tyramine treatment enhanced the adhesion of the small pore size scaffold to osteochondral tissue and increased glycosaminoglycan and collagen type II (Col II) contents, while reducing collagen type X (Col X) production in the cartilage layer. Col X content was higher for scaffolds with a large pore size, which was accompanied by the enhanced generation of subchondral bone. Thus, chondrocytes seeded in tyramine-treated bilayered scaffolds with small and large pores in the upper and lower parts, respectively, can promote osteochondral regeneration and integration for articular cartilage repair.


Assuntos
Cartilagem Articular/citologia , Condrócitos/citologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Regeneração , Engenharia Tecidual/métodos , Alicerces Teciduais/química , Tiramina/química , Animais , Materiais Biocompatíveis/química , Colágeno/metabolismo , Força Compressiva , Modelos Animais , Espectroscopia Fotoeletrônica , Porosidade , Propriedades de Superfície , Suínos , Água/química
9.
J Exp Bot ; 69(22): 5389-5401, 2018 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-30165491

RESUMO

As key mediators linking developmental processes with plant immunity, TCP (TEOSINTE-BRANCHED, CYCLOIDEA, PROLIFERATION FACTOR 1 and 2) transcription factors have been increasingly shown to be targets of pathogenic effectors. We report here that TB/CYC (TEOSINTE-BRANCHED/CYCLOIDEA)-TCPs are destabilized by phytoplasma SAP11 effectors, leading to the proliferation of axillary meristems. Although a high degree of sequence diversity was observed among putative SAP11 effectors identified from evolutionarily distinct clusters of phytoplasmas, these effectors acquired fundamental activity in destabilizing TB/CYC-TCPs. In addition, we demonstrate that miR156/SPLs and miR172/AP2 modules, which represent key regulatory hubs involved in plant phase transition, were modulated by Aster Yellows phytoplasma strain Witches' Broom (AY-WB) protein SAP11. A late-flowering phenotype with significant changes in the expression of flowering-related genes was observed in transgenic Arabidopsis plants expressing SAP11AYWB. These morphological and molecular alterations were correlated with the ability of SAP11 effectors to destabilize CIN (CINCINNATA)-TCPs. Although not all putative SAP11 effectors display broad-spectrum activities in modulating morphological and physiological changes in host plants, they serve as core virulence factors responsible for the witches' broom symptom caused by phytoplasmas.


Assuntos
Proteínas de Arabidopsis/genética , Arabidopsis/genética , Phytoplasma/fisiologia , Fatores de Transcrição/genética , Arabidopsis/anatomia & histologia , Arabidopsis/metabolismo , Arabidopsis/virologia , Proteínas de Arabidopsis/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Phytoplasma/genética , Imunidade Vegetal/genética , Plantas Geneticamente Modificadas/anatomia & histologia , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/metabolismo , Plantas Geneticamente Modificadas/virologia , Fatores de Transcrição/metabolismo , Fatores de Virulência
10.
Exp Brain Res ; 236(5): 1395-1407, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29536148

RESUMO

One of the characteristic features of the human motor system is redundancy-i.e., the ability to achieve a given task outcome using multiple coordination patterns. However, once participants settle on using a specific coordination pattern, the process of learning to use a new alternative coordination pattern to perform the same task is still poorly understood. Here, using two experiments, we examined this process of how participants shift from one coordination pattern to another using different reinforcement schedules. Participants performed a virtual reaching task, where they moved a cursor to different targets positioned on the screen. Our goal was to make participants use a coordination pattern with greater trunk motion, and to this end, we provided reinforcement by making the cursor disappear if the trunk motion during the reach did not cross a specified threshold value. In Experiment 1, we compared two reinforcement schedules in two groups of participants-an abrupt group, where the threshold was introduced immediately at the beginning of practice; and a gradual group, where the threshold was introduced gradually with practice. Results showed that both abrupt and gradual groups were effective in shifting their coordination patterns to involve greater trunk motion, but the abrupt group showed greater retention when the reinforcement was removed. In Experiment 2, we examined the basis of this advantage in the abrupt group using two additional control groups. Results showed that the advantage of the abrupt group was because of a greater number of practice trials with the desired coordination pattern. Overall, these results show that reinforcement can be successfully used to shift coordination patterns, which has potential in the rehabilitation of movement disorders.


Assuntos
Retroalimentação Fisiológica/fisiologia , Aprendizagem/fisiologia , Movimento/fisiologia , Desempenho Psicomotor/fisiologia , Reforço Psicológico , Feminino , Humanos , Masculino , Adulto Jovem
11.
Tohoku J Exp Med ; 243(3): 187-193, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-29176262

RESUMO

Acute lung injury (ALI) is one of the complications of severe sepsis, causing sudden deaths. However, information regarding predictive factors for the onset of ALI in severe sepsis is limited. Growth arrest-specific gene 6 (Gas6) is secreted by endothelial cells and is important for the activation of endothelium during inflammation. This study aimed to investigate the predictive effect of plasma Gas6 in patients with severe sepsis. Collection of plasma samples was carried out from 129 participants with severe sepsis following with or without ALI development. We found that the elevated levels of Gas6, interleukin-6 and -8 (IL-6 and IL-8) in plasma were associated with the ALI development (P = 0.003, 0.002, and 0.004, respectively). We also observed the robust correlation between the plasma level of Gas6 and the following ALI development to adjustment for sepsis and administration of vasopressor. Between patients with ALI (n = 18) and those without ALI (n = 111), Gas6 and the Lung Injury Prediction Score (LIPS) showed promising discrimination (AUROC, 0.74 and 0.68, respectively), and in combination with these two indexes, the AUROC was increased to 0.86 (vs. 0.74, P = 0.05), while soluble receptor for advanced glycation end products (sRAGE) and Willebrand factor (vWF) in plasma showed no predictive value for of ALI. Collectively, our findings indicate that higher levels of Gas6 in plasma are obviously correlated with ALI development. An early increase in the plasma Gas6 level suggests that endothelial injury is a key link in the pathogenesis of ALI.


Assuntos
Lesão Pulmonar Aguda/sangue , Lesão Pulmonar Aguda/complicações , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Sepse/complicações , Sepse/diagnóstico , Lesão Pulmonar Aguda/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Sepse/sangue
13.
Electrophoresis ; 34(2): 297-303, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23161197

RESUMO

This study examines the use of unmodified magnetite nanoparticles (Fe(3)O(4) NPs) for selective extraction and enrichment of the catecholamines dopamine (DA), noradrenaline (NE), and adrenaline (E), prior to analysis using capillary electrophoresis with UV detection. Coordination between Fe(3+) on-the-surface Fe(3)O(4) NPs and the catechol moiety of catecholamines enables Fe(3)O(4) NPs to capture catecholamines from an aqueous solution. We obtained maximum loading of catecholamines on the NP surface by adjusting the pH of the solution to 7.0. In addition, catecholamine loading on the Fe(3)O(4) NPs increased in conjunction with NP concentrations. H(3)PO(4) was found to be efficient for the removal of adsorbed catecholamines on the NP surface. Adding 1.2% poly(diallyldimethylammonium chloride) to the background electrolyte resulted in a baseline separation of the liberated catecholamines within 20 min. Under optimal extraction and separation conditions, the limit of detections at a S/N ratio of 3 for E, NE, and DA were 9, 8, and 10 nM, respectively. Significantly, the combination of a phenylboronate-containing spin column and the proposed method was successfully applied to the determination of NE and DA in human urine and NE in Portulaca oleracea L. leaves.


Assuntos
Catecolaminas/isolamento & purificação , Eletroforese Capilar/métodos , Nanopartículas de Magnetita/química , Adulto , Catecolaminas/análise , Catecolaminas/urina , Humanos , Masculino , Extratos Vegetais/química , Folhas de Planta/química , Portulaca/química , Reprodutibilidade dos Testes , Espectrofotometria Ultravioleta
14.
Front Cardiovasc Med ; 10: 1132062, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37456820

RESUMO

Background: We aimed to evaluate the efficacy and safety of the 'jailed semi-inflated balloon technique' (JSIBT) for side branch (SB) protection in STEMI patients with a culprit lesion involving a coronary artery bifurcation while undergoing emergent percutaneous coronary intervention (PCI). Methods: We treated between Jan, 2011 and Jun, 2020, a total of 264 STEMI patients with a culprit lesion that involved a coronary artery bifurcation using primary PCI. In 30 patients, SB was protected by JSIBT (the JSIBT group). In 234 patients, SB was either protected or not protected by a placed wire (the non-JSIBT group). Results: In both groups, after PCI procedure, TIMI flows of main vessel (MV) and SB were increased significantly compared with their measurements before the procedure. TIMI flows of post-procedural MV were similar between the two groups. In the JSIBT group, TIMI flows of SB both peri-procedure and post-procedure measurements were significantly greater than the non-JSIBT group. Despite a higher incidence of SB dissection in the JSIBT group, no inter-group difference was found in their total SB complications (like SB dissection, SB occlusion, wire entrapment or balloon rupture/entrapment). While JSIBT was an independent predictor for the SB TIMI 3 flow measured at the end of primary PCI, it was not an independent predictor for SB complications. Conclusion: The use of JSIBT as a method of SB protection during primary PCI not only provided better SB protection, but it also had a similar rate of SB complications compared with those with or without prior application of SB wire. This technique may be an effective method of protecting SB for STEMI patients involving coronary artery bifurcation and underwent emergent PCI.

15.
In Vivo ; 37(5): 1991-2000, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37652472

RESUMO

BACKGROUND/AIM: Immunotherapy has been considered a promising approach for brain tumor treatment since the discovery of the brain lymphatic system. Glioblastoma (GBM), the most aggressive type of brain tumor, is associated with poor prognosis and a lack of effective treatment options. MATERIALS AND METHODS: To test the efficacy of human anti-PD-1, we used a humanized PD-1 knock-in mouse to establish an orthotopic GBM-bearing model. RESULTS: Nivolumab, a human anti-PD-1, effectively inhibited tumor growth, increased the survival rate of mice, enhanced the accumulation and function of cytotoxic T cells, reduced the accumulation and function of immunosuppressive cells and their related factors, and did not induce tissue damage or biochemical changes. The treatment also induced the accumulation and activation of CD8+ cytotoxic T cells, while reducing the accumulation and activation of myeloid-derived suppressor cells, regulatory T cells, and tumor-associated macrophages in the immune microenvironment. CONCLUSION: Nivolumab has the potential to be a treatment for GBM.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Humanos , Animais , Camundongos , Glioblastoma/tratamento farmacológico , Glioblastoma/genética , Nivolumabe/farmacologia , Receptor de Morte Celular Programada 1 , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Encéfalo/patologia , Imunoterapia , Linhagem Celular Tumoral , Microambiente Tumoral
16.
J Neural Eng ; 19(5)2022 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-36198278

RESUMO

Objective. Despite the tremendous promise of invasive brain-computer interfaces (iBCIs), the associated study costs, risks, and ethical considerations limit the opportunity to develop and test the algorithms that decode neural activity into a user's intentions. Our goal was to address this challenge by designing an iBCI model capable of testing many human subjects in closed-loop.Approach. We developed an iBCI model that uses artificial neural networks (ANNs) to translate human finger movements into realistic motor cortex firing patterns, which can then be decoded in real time. We call the model the joint angle BCI, or jaBCI. jaBCI allows readily recruited, healthy subjects to perform closed-loop iBCI tasks using any neural decoder, preserving subjects' control-relevant short-latency error correction and learning dynamics.Main results. We validated jaBCI offline through emulated neuron firing statistics, confirming that emulated neural signals have firing rates, low-dimensional PCA geometry, and rotational jPCA dynamics that are quite similar to the actual neurons (recorded in monkey M1) on which we trained the ANN. We also tested jaBCI in closed-loop experiments, our single study examining roughly as many subjects as have been tested world-wide with iBCIs (n= 25). Performance was consistent with that of the paralyzed, human iBCI users with implanted intracortical electrodes. jaBCI allowed us to imitate the experimental protocols (e.g. the same velocity Kalman filter decoder and center-out task) and compute the same seven behavioral measures used in three critical studies.Significance. These encouraging results suggest the jaBCI's real-time firing rate emulation is a useful means to provide statistically robust sample sizes for rapid prototyping and optimization of decoding algorithms, the study of bi-directional learning in iBCIs, and improving iBCI control.


Assuntos
Interfaces Cérebro-Computador , Córtex Motor , Algoritmos , Eletrodos Implantados , Humanos , Córtex Motor/fisiologia , Movimento
17.
Front Cardiovasc Med ; 9: 846564, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35369302

RESUMO

Background: Rotational atherectomy (RA) is an indispensable tool used for calcified lesion preparation in percutaneous coronary intervention (PCI). However, use of RA in the setting of acute myocardial infarction (AMI) is challenged with limited clinical data. Objectives: This study aims to retrospectively investigate the procedural results, periprocedural complications, and clinical outcomes of RA in patients with AMI. Methods: All possible consecutive patients who received RA in AMI from January 2009 to March 2018 in a single tertiary center were analyzed retrospectively. Patients without AMI during the study period were also enrolled for comparison. Results: A total of 121 patients with AMI (76.0 ± 10.8 years, 63.6% males) and 290 patients without AMI were recruited. Among the AMI group, 81% of patients had non-ST-elevation myocardial infarction (NSTEMI) and 14% presented with cardiogenic shock. RA could be completed in 98.8% of patients in the AMI group and 98.3% in the non-AMI group (p = 1.00). The periprocedural complication rates were comparable between the AMI and non-AMI groups. The risks of in-hospital, 30-day, 90-day, and 1-year cardiovascular major adverse cardiac events (CV MACE) were significantly higher in the AMI group compared with the non-AMI group (in-hospital 13.2 vs. 2.8%, p < 0.001; 30-day 14.2 vs. 4.5%, p < 0.001; 90-day 20.8 vs. 6.9%, p < 0.001; 1-year 30.8 vs. 19.1%, p = 0.01). AMI at initial presentation and cardiogenic shock were predictors for both in-hospital CV MACE and 1-year CV MACE in multivariable binary logistic regression analysis. Other predictors for 1-year CV MACE included serum creatinine level and triple vessel disease. Conclusion: RA in patients with AMI is feasible with a high procedural completion rate and acceptable periprocedural complications. Given unstable hemodynamics and complex coronary anatomy, the in-hospital and 1-year MACE rates remained higher in patients with AMI compared with patients without AMI.

18.
Cells ; 10(12)2021 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-34944042

RESUMO

Cartilage stem/progenitor cells (CSPCs) are cartilage-specific, multipotent progenitor cells residing in articular cartilage. In this study, we investigated the characteristics and potential of human CSPCs combined with poly(lactic-co-glycolic acid) (PLGA) scaffolds to induce osteochondral regeneration in rabbit knees. We isolated CSPCs from human adult articular cartilage undergoing total knee replacement (TKR) surgery. We characterized CSPCs and compared them with infrapatellar fat pad-derived stem cells (IFPs) in a colony formation assay and by multilineage differentiation analysis in vitro. We further evaluated the osteochondral regeneration of the CSPC-loaded PLGA scaffold during osteochondral defect repair in rabbits. The characteristics of CSPCs were similar to those of mesenchymal stem cells (MSCs) and exhibited chondrogenic and osteogenic phenotypes without chemical induction. For in vivo analysis, CSPC-loaded PLGA scaffolds produced a hyaline-like cartilaginous tissue, which showed good integration with the host tissue and subchondral bone. Furthermore, CSPCs migrated in response to injury to promote subchondral bone regeneration. Overall, we demonstrated that CSPCs can promote osteochondral regeneration. A monophasic approach of using diseased CSPCs combined with a PLGA scaffold may be beneficial for repairing complex tissues, such as osteochondral tissue.


Assuntos
Cartilagem Articular/citologia , Diferenciação Celular , Condrogênese , Células-Tronco/citologia , Alicerces Teciduais/química , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Regeneração Óssea , Linhagem da Célula , Forma Celular , Células Cultivadas , Ensaio de Unidades Formadoras de Colônias , Humanos , Imunofenotipagem , Masculino , Pessoa de Meia-Idade , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Porosidade , Coelhos , Microtomografia por Raio-X
19.
Medicine (Baltimore) ; 100(3): e23830, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33545949

RESUMO

ABSTRACT: The treatment of patients with multivessel coronary artery disease (MVD) by coronary stenting (PCI) and the "gold standard" conventional coronary-artery bypass grafting (C-CABG) has been well explored in the literature. However, the clinical outcomes of robot-assisted CABG (R-CABG) vs C-CABG in MVD patients in real-world practice were unknown. We aimed to study the clinical outcomes of MVD patients who underwent R-CABG (robotic MIDCAB) and C-CABG at our institution between January 2005 and December 2013.A total of 516 MVD patients received CABG were recruited into this study. Among them, 281 patients received R-CABG and 235 patients underwent C-CABG. Patients in the R-CABG group were younger, and had fewer vessels with coronary artery disease (CAD), lower prevalence of chronic renal disease (CKD), higher left ventricular ejection fraction (LVEF), as well as lower Euro scores. The in-hospital and long-term mortalities were lower in the R-CABG group, but the incidences of target lesion revascularization (TLR), target vessel revascularization (TVR), myocardial infarction (MI), and stroke were not significantly different between the two groups. The long-term mortality was related to age, lower LVEF, and CKD, but not residual SYNTAX score, or completeness of revascularization. The revascularization modality (R-CABG vs C-CABG) was a borderline significantly independent predictor of long-term mortality (OR 1.76 [0.99-3.14], P = .055).Our study concluded that R-CABG, in comparison with C-CABG, for MVD carried out in younger patients involved fewer clinical complexities was associated with lower in-hospital and long-term mortalities in real-world practice. However, the long-term rates of TLR, TVR, MI, and stroke were similar. The long-term mortality was correlated with age, lower LVEF, and CKD, where R-CABG remained a borderline significant predictor after correcting for confounding factors. R-CABG could be an effective alternative to C-CABG for MVD patients with fewer clinical complexities in real-world practice.


Assuntos
Ponte de Artéria Coronária , Doença da Artéria Coronariana/cirurgia , Procedimentos Cirúrgicos Robóticos , Idoso , Angiografia por Tomografia Computadorizada , Doença da Artéria Coronariana/diagnóstico por imagem , Feminino , Humanos , Masculino , Prontuários Médicos , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Resultado do Tratamento
20.
Medicine (Baltimore) ; 99(3): e18796, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32011481

RESUMO

RATIONALE: Type A aortic dissection (TAAD) is a life-threatening disorder yet it is hard to diagnose. The dissection might extend to the coronary artery causing ST-segment elevation myocardial infarction (STEMI). Physicians might not recognize this particularly early in its presentation and patients proceed to receive the primary percutaneous coronary intervention. We present such a case and found that the marked pressure difference between the radial and ascending aortae could be a useful clue for diagnosing the aortic dissection-related myocardial infarction. PATIENT CONCERNS: A 58-year-old male was presented to our emergency department for the complaint of left side chest pain that lasted for an hour with concomitant hypotension. STEMI was diagnosed at that time. DIAGNOSIS: The emergent primary percutaneous intervention was performed. When the diagnostic catheter was advanced to the ascending aorta, the systolic aorta pressure became 20 mm Hg higher than radial systolic pressure. Due to the abnormally large pressure differential between the peripheral radial artery and central ascending aorta, TAAD was suspected. INTERVENTIONS: After angiography and computer tomography confirmed the diagnosis of TAAD, the patient was sent for emergent surgery. OUTCOMES: The patient was died because of extensive dissection and shock. LESSONS: We present such a case and found that the marked pressure difference between the radial and ascending aortae during catheterization could be a useful clue for diagnosing the aortic dissection-related myocardial infarction. This clue had hinted our speedy examination of the occluded coronary artery and dissection flap, and led to an early and accurate diagnosis.


Assuntos
Dissecção Aórtica/complicações , Dissecção Aórtica/diagnóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/etiologia , Dissecção Aórtica/cirurgia , Aorta , Pressão Sanguínea , Catéteres , Evolução Fatal , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia
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