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1.
J Orthop Surg (Hong Kong) ; 32(2): 10225536241254208, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38744697

RESUMEN

BACKGROUND: Chordoma is a bone tumor that tends to occur in middle-aged and elderly people. It grows relatively slowly but is aggressive. The prognosis of middle-aged and elderly patients with chordoma is quite different from that of young patients with chordoma. OBJECTIVES: The purpose of the research was to construct a nomogram to predict the Individualized prognosis of middle-aged and elderly (age greater than or equal to 40 years) patients with chordoma. METHODS: In this study, we screened 658 patients diagnosed with chordoma from 1983 to 2015 in the Surveillance, Epidemiology, and End Results (SEER) database. We determined the independently prognostic factors that affect the survival of patients by univariate and multivariate Cox proportional hazards model. Based on the independent prognostic factors, we constructed a nomogram to predict the overall survival (OS) rates of middle-aged and elderly patients with chordoma at 3 and 5 years. The validation of this nomogram was completed by evaluating the calibration curve and the C-index. RESULTS: We screened a total of 658 patients and divided them into two cohort. Training cohort had 462 samples and validation cohort had 196 samples. The multivariate Cox proportional hazards model of the training group showed an association of age, tumor size, histology, primary site, surgery, and extent of disease with OS rates. Based on these results, we constructed the corresponding nomogram. The calibration curve and C-index showed the satisfactory ability of the nomogram in terms of predictive ability. CONCLUSION: Nomogram can be an effective prognostic tool to assess the prognosis of middle-aged and elderly patients with chordoma and can help clinicians in medical decision-making and enable patients to receive more accurate and reasonable treatment.


Asunto(s)
Neoplasias Óseas , Cordoma , Nomogramas , Programa de VERF , Humanos , Cordoma/mortalidad , Cordoma/patología , Cordoma/terapia , Masculino , Femenino , Persona de Mediana Edad , Anciano , Pronóstico , Neoplasias Óseas/mortalidad , Neoplasias Óseas/patología , Neoplasias Óseas/terapia , Neoplasias Óseas/epidemiología , Adulto , Tasa de Supervivencia , Modelos de Riesgos Proporcionales , Factores de Edad , Anciano de 80 o más Años
2.
Curr Atheroscler Rep ; 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38709435

RESUMEN

PURPOSE OF REVIEW: Abdominal aortic aneurysm refers to a serious medical condition that can cause the irreversible expansion of the abdominal aorta, which can lead to ruptures that are associated with up to 80% mortality. Currently, surgical and interventional procedures are the only treatment options available for treating abdominal aortic aneurysm patients. In this review, we focus on the upstream and downstream molecules of the microRNA-related signaling pathways and discuss the roles, mechanisms, and targets of microRNAs in abdominal aortic aneurysm modulation to provide novel insights for precise and targeted drug therapy for the vast number of abdominal aortic aneurysm patients. RECENT FINDINGS: Recent studies have highlighted that microRNAs, which are emerging as novel regulators of gene expression, are involved in the biological activities of regulating abdominal aortic aneurysms. Accumulating studies suggested that microRNAs modulate abdominal aortic aneurysm development through various signaling pathways that are yet to be comprehensively summarized. A total of six signaling pathways (NF-κB signaling pathway, PI3K/AKT signaling pathway, MAPK signaling pathway, TGF-ß signaling pathway, Wnt signaling pathway, and P53/P21 signaling pathway), and a total of 19 miRNAs are intimately associated with the biological properties of abdominal aortic aneurysm through targeting various essential molecules. MicroRNAs modulate the formation, progression, and rupture of abdominal aortic aneurysm by regulating smooth muscle cell proliferation and phenotype change, vascular inflammation and endothelium function, and extracellular matrix remodeling. Because of the broad crosstalk among signaling pathways, a comprehensive analysis of miRNA-mediated signaling pathways is necessary to construct a well-rounded upstream and downstream regulatory network for future basic and clinical research of AAA therapy.

3.
Cell Biochem Funct ; 42(2): e3985, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38509716

RESUMEN

Autophagy is a process in which cells degrade intracellular substances and play a variety of roles in cells, such as maintaining intracellular homeostasis, preventing cell overgrowth, and removing pathogens. It is highly conserved during the evolution of eukaryotic cells. So far, the study of autophagy is still a hot topic in the field of cytology. Ferroptosis is an iron-dependent form of cell death, accompanied by the accumulation of reactive oxygen species and lipid peroxides. With the deepening of research, it has been found that ferroptosis, like autophagy, is involved in the occurrence and development of cardiovascular diseases. The relationship between autophagy and ferroptosis is complex, and the association between the two in cardiovascular disease remains to be clarified. This article reviews the mechanism of autophagy and ferroptosis and their correlation, and discusses the relationship between them in cardiovascular diseases, which is expected to provide new and important treatment strategies for cardiovascular diseases.


Asunto(s)
Enfermedades Cardiovasculares , Ferroptosis , Humanos , Hierro/metabolismo , Muerte Celular , Especies Reactivas de Oxígeno/metabolismo , Autofagia
4.
Free Radic Biol Med ; 216: 106-117, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38461872

RESUMEN

Oxidized low density lipoprotein (oxLDL)-induced endothelial oxidative damage promotes the development of atherosclerosis. Caveolae play an essential role in maintaining the survival and function of vascular endothelial cell (VEC). It is reported that the long coiled-coil protein NECC2 is localized in caveolae and is associated with neural cell differentiation and adipocyte formation, but its role in VECs needs to be clarified. Our results showed NECC2 expression increased in the endothelium of plaque-loaded aortas and oxLDL-treated HUVECs. Down-regulation of NECC2 by NECC2 siRNA or compound YF-307 significantly inhibited oxLDL-induced VEC apoptosis and the adhesion factors expression. Remarkably, inhibition of NECC2 expression in the endothelium of apoE-/- mice by adeno-associated virus (AAV)-carrying NECC2 shRNA or compound YF-307 alleviated endothelium injury and restricted atherosclerosis development. The immunoprecipitation results confirmed that NECC2 interacted with Tyk2 and caveolin-1(Cav-1) in VECs, and NECC2 further promoted the phosphorylation of Cav-1 at Tyr14 b y activating Tyk2 phosphorylation. On the other hand, inhibiting NECC2 levels suppressed oxLDL-induced phosphorylation of Cav-1, uptake of oxLDL by VECs, accumulation of intracellular reactive oxygen species and activation of NF-κB. Our findings suggest that NECC2 may contribute to oxLDL-induced VEC injury and atherosclerosis via modulating Cav-1 phosphorylation through Tyk2. This work provides a new concept and drug target for treating atherosclerosis.


Asunto(s)
Aterosclerosis , Animales , Ratones , Apolipoproteínas/efectos adversos , Apolipoproteínas/metabolismo , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo , Aterosclerosis/metabolismo , Endotelio/metabolismo , Lipoproteínas LDL/metabolismo , Estrés Oxidativo
5.
Cell Biochem Funct ; 42(2): e3955, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38379220

RESUMEN

Heart diseases remain the primary cause of human mortality in the world. Although conventional therapeutic opportunities fail to halt or recover cardiac fibrosis, the promising clinical results and therapeutic efficacy of engineered chimeric antigen receptor (CAR) T cell therapy show several advancements. However, the current models of CAR-T cells need further improvement since the T cells are associated with the triggering of excessive inflammatory cytokines that directly affect cardiac functions. Thus, the current study highlights the critical function of heart immune cells in tissue fibrosis and repair. The study also confirms CAR-T cell as an emerging therapeutic for treating cardiac fibrosis, explores the current roadblocks to CAR-T cell therapy, and considers future outlooks for research development.


Asunto(s)
Receptores Quiméricos de Antígenos , Humanos , Receptores Quiméricos de Antígenos/uso terapéutico , Inmunoterapia Adoptiva/métodos , Linfocitos T
6.
ESC Heart Fail ; 11(1): 574-580, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37909849

RESUMEN

Patients with multiple myeloma (MM) are likely to achieve poor therapeutic response when organs are involved. We produced anti-B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR)-T cells, which are in a trial for patients with relapsed/refractory MM. One enrolled patient developed severe heart failure, highly suspected as light chain cardiac amyloidosis. He exhibited increased N-terminal pro-brain natriuretic peptide with a peak of 32 299 ng/mL and heart failure with an ejection fraction of 30%. Anti-BCMA CAR-T cells were administered following lymphodepletion. The patient achieved cardiac response within 1 week with a decrease in N-terminal pro-brain natriuretic peptide by 80%, an increase in ejection fraction from 30% to 56%, and a haematological response with negative minimal residual disease at 1 month and a complete response at 1 year. To date, this patient has maintained good health without heart failure or haematological relapse. Herein, we show the efficacy of anti-BCMA CAR-T cells in patients with MM and severe heart failure.


Asunto(s)
Insuficiencia Cardíaca , Mieloma Múltiple , Receptores Quiméricos de Antígenos , Masculino , Humanos , Mieloma Múltiple/terapia , Mieloma Múltiple/tratamiento farmacológico , Receptores Quiméricos de Antígenos/uso terapéutico , Antígeno de Maduración de Linfocitos B/uso terapéutico , Péptido Natriurético Encefálico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Insuficiencia Cardíaca/terapia , Insuficiencia Cardíaca/tratamiento farmacológico
7.
J Diabetes Complications ; 38(1): 108671, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-38154217

RESUMEN

AIMS: Growing preclinical and clinical evidence has suggested the potential method of umbilical cord mesenchymal stem cell (UCMSC) therapy for diabetic foot. Thus, the authors provided an outline of the application of UCMSCs in the treatment of diabetic foot and further summarized the roles and mechanisms of this therapy. DATA SYNTHESIS: With no time limitations, the authors searched the Web of Science, Cochrane Central Register of Controlled Trials, and PubMed (MEDLINE) databases. 14 studies were included, including 9 preclinical experiments and 5 clinical trials (3 RCTs and 2 single-arm trials). CONCLUSIONS: The UCMSCs are of great efficacy and safety, and function mainly by reducing inflammation, regulating immunity, promoting growth factors, and enhancing the functions of vascular endothelial cells, fibroblasts, and keratinocytes. As a result, ulcer healing-related biological processes ensue, which finally lead to diabetic foot ulcer healing and clinical symptom improvement. UCMSC treatment enhances diabetic foot ulcer healing and has a safety profile. They function mainly by modulating immunity, promoting growth factor secretion, and enhancing cellular functions. More well-designed preclinical and clinical studies are needed to provide the most optimal protocol, the comprehensive molecular mechanisms, as well as to further evaluate the efficiency and safety profile of UCMSC treatment in diabetic foot patients.


Asunto(s)
Pie Diabético , Células Madre Mesenquimatosas , Humanos , Pie Diabético/metabolismo , Células Endoteliales , Cicatrización de Heridas
8.
J Endovasc Ther ; : 15266028231210221, 2023 Nov 19.
Artículo en Inglés | MEDLINE | ID: mdl-37981803

RESUMEN

OBJECTIVE: The objective of this study was to introduce our institutional experience of treatment strategies (cervical subclavian artery reconstruction, thoracotomy subclavian artery reconstruction and endovascular treatment) for proximal isolated subclavian artery aneurysms (PISAAs). METHODS: we retrospectively analyzed 15 consecutive patients with PISAAs treated by different treatment strategies (cervical reconstruction, thoracotomy reconstruction and endovascular treatment) in our institution from May 2016 to May 2022. Baseline data, surgery-related data, postoperative information and long-term follow-up were assessed. RESULTS: A total of 17 PISAAs in 15 consecutive patients were treated in our institution. The success rates of subclavian artery reconstruction in the cervical reconstruction, the thoracotomy reconstruction and the endovascular treatment were 100%, 100 and 83.33%, respectively. About the involved vertebral artery, the reconstruction rates in the cervical reconstruction, the thoracotomy reconstruction, and the endovascular treatment were 80%, 75%, and 0, respectively. The intraoperative blood loss in the thoracotomy reconstruction was significantly higher than that in the cervical reconstruction and the endovascular treatment (p<0.05). The total operation time of the thoracotomy reconstruction was significantly longer than that of the cervical reconstruction and the endovascular treatment (p<0.05). In terms of postoperative ventilator use time, total postoperative drainage fluid, total postoperative drainage time, and ICU duration, both the thoracotomy reconstruction and the cervical reconstruction were significantly more than the endovascular treatment (p<0.05). During the follow-up, one patient in the endovascular treatment underwent re-intervention 22 months after surgery due to in-stent occlusion. CONCLUSIONS: For patients with PISAAs, different treatment strategies are recommended depending on the size of the aneurysms and whether the involved vertebral arteries require reconstruction. CLINICAL IMPACT: This article is the largest study on the treatment strategies of PISAAs. By comparing the prognosis and complications of endovascular treatment with those of open surgery, it provides a certain reference basis for the choice of treatment for patients with PISAAs. For patients with aneurysms' diameter of >50 mm, the thoracotomy subclavian artery reconstruction is recommended; for patients with aneurysms' diameter of <30 mm requiring reconstruction of the involved vertebral arteries, the cervical subclavian artery reconstruction is recommended; for patients with aneurysms' diameter of <30 mm not requiring reconstruction of the involved vertebral arteries, the endovascular treatment is recommended.

9.
Exp Ther Med ; 26(4): 471, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37664681

RESUMEN

The present study aimed to study the efficacy and adverse effects of anti-B-cell maturation antigen (BCMA) chimeric antigen receptor T (CAR-T) cell therapy in relapsed or refractory multiple myeloma. Patients were divided into three dose groups based on cell therapy concentration. After CAR-T cell therapy for 10 patients with recurrent or refractory multiple myeloma, the patients were monitored and evaluated regularly to observe the efficacy and adverse reactions of CAR-T cell therapy. At a median follow-up of 337 (253-504) days, one patient succumbed 24 days due to rapidly progressing disease. The overall response rate of nine patients was 88.9%, including 77.8% (7/9) with minimal residual disease negative complete remission (CR) and 11.1% (1/9) with partial remission. A total of three patients were maintained in remission state for more than a year and eight were maintained for more than six months. Among the three patients with extramedullary invasion, two extramedullary lesions disappeared and one was stable. The highest copy number of CAR-T cells in seven patients with CR was >1x105 copies/µl gDNA, and the best therapeutic effect can be achieved within 30 (7-30) days after the copy number of CAR-T cells reached 1x105 copies/µl genomic DNA. The median onset time in the nine patients was 43 (22-169) days, and the median progression-free survival was 337 (253-504). Among the 10 patients, nine (90%) had cytokine release syndrome, all of which were below grade II. There were nine (90%) patients with hematological adverse reactions, six (60%) patients with severe anemia, five (50%) patients with grade III and above leukopenia, five (50%) patients with granulocytopenia, four (40%) patients with grade III and above thrombocytopenia, and three (30%) patients with grade III and above pancytopenia. It was concluded that anti-BCMA CAR-T cell therapy is a promising treatment method for relapsed or refractory multiple myeloma and extramedullary invasion, with stable efficacy and controllable adverse effects.

10.
J Cancer Res Clin Oncol ; 149(17): 16213-16229, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37682360

RESUMEN

BACKGROUND: Breast cancer is considered the number one killer of women both in China and abroad, and the leading cause of cancer death. It severely affects female health-related quality of life. Broad-complex, tramtrack, bric à brac (BTB) protein family was first discovered in drosophila as early as in 1993 by Godt D and peers, since then, more family members and their critical biological functions were uncovered. Moreover, researchers around the world have recently demonstrated that numerous signaling pathways connect BTB family members and human breast cancer. PURPOSE: In this review, we critically discuss these findings regarding the essential mechanisms and functions of the BTB protein family in mediating the organic processes of human breast cancer. Meanwhile, we summarize the signaling pathways the BTB protein family participates in. And we address that BTB proteins regulate the growth, apoptosis, and other behaviors of breast cancer cells. We also point out the future directions for further studies in this field. METHODS: The relevant online literatures have been reviewed for this article. CONCLUSION: This review could offer an update on novel molecular targets for treating human breast cancer and new insights into BTB protein family research.


Asunto(s)
Neoplasias de la Mama , Animales , Humanos , Femenino , Calidad de Vida , Drosophila , China
11.
J Orthop Surg (Hong Kong) ; 31(2): 10225536231174255, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37147017

RESUMEN

BACKGROUND: The incidence of chondrosarcoma is increasing every year, and the treatment and prognosis of patients with high-grade chondrosarcoma are becoming more and more important. Nomogram is a tool that can quickly and easily predict the overall survival of tumor patients. Therefore, the development and validation of a nomogram to predict overall survival in patients with high-grade chondrosarcoma was desired. METHODS: We retrospectively collected 396 patients with high-grade chondrosarcoma from the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2015. Randomly divided into model and validation groups, the best cut-off values for age and tumor size grouping were derived by using X-tile software. Then, independent prognostic factors for high-grade chondrosarcoma were derived by SPSS.26 univariate and multivariate Cox analyses analysis in the model group, and the model was evaluated by using R software, using C-indix and ROC curves, and finally these independent prognostic factors were included in Nomogram. RESULTS: 396 patients were randomly assigned to the modelling group (n = 280) or the validation group (n = 116). Age, tissue-type, tumor size, AJCC stage, regional expansion and surgery were identified as independent prognostic factors (p < 0.05) which further combined to construct a nomogram. The C-index of internal validation for overall survival(OS) was 0.757, while the C-index of external validation for overall survival(OS) was 0.832. Both internal and external calibration curves show a good agreement between nomogram prediction and actual survival. CONCLUSION: In this study, we established age, tumour size, AJCC stage, tissue type, surgery and tumor extension as independent prognostic factors for high-grade chondrosarcoma and constructed a nomogram to predict 3- and 5-year survival rates for high-grade chondrosarcoma.


Asunto(s)
Neoplasias Óseas , Condrosarcoma , Humanos , Neoplasias Óseas/epidemiología , Condrosarcoma/epidemiología , Nomogramas , Pronóstico , Estudios Retrospectivos
12.
J Mol Histol ; 54(1): 67-75, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36719565

RESUMEN

Extracellular matrix (ECM) production and nucleus pulposus (NP) cell migration increase under periodic mechanical stress (PMS), but the underpinning regulatory mechanism remains unclear. This work aimed to examine the regulatory effects of cytoskeleton-lipid raft-integrin α1 signaling in NP cells exposed to PMS. Briefly, In NP cells, cytoskeleton rearrangement, lipid raft aggregation and integrin α1 expression in the stress and control groups were assessed by immunofluorescent staining and immunoblot. In addition, cell migration and ECM gene expression were detected by a scratch test and quantitative reverse transcription polymerase chain reaction (qRT­PCR), respectively. As a result, PMS up-regulated ECM gene expression and enhanced NP cell migration (both P < 0.05), accompanied by increased integrin α1, lipid raft, caveolin-3, F-actin and ß-tubulin amounts. Pretreatment with the lipid raft inhibitor methyl-ß-cyclodextrin (MßCD) or small interfering RNA (siRNA) targeting caveolin-3 resulted in decreased ECM mRNA synthesis and cell migration induced by PMS (both P < 0.05); meanwhile, integrin α1 expression was also reduced. F-actin and ß-tubulin inhibition by cytochalasin D and colchicine, respectively, not only reduced ECM mRNA synthesis and cell migration (both P < 0.05), but also disrupted lipid raft and caveolin-3 amount increases induced by PMS in NP cells. In conclusion, PMS promotes ECM mRNA up-regulation and cell migration through the cytoskeleton-lipid raft-integrin α1 signaling pathway, inhibiting cytoskeleton and lipid rafts could block the cellular effects.


Asunto(s)
Actinas , Núcleo Pulposo , Ratas , Animales , Actinas/metabolismo , Integrina alfa1/metabolismo , Tubulina (Proteína)/metabolismo , Tubulina (Proteína)/farmacología , Estrés Mecánico , Núcleo Pulposo/metabolismo , Caveolina 3/metabolismo , Citoesqueleto/metabolismo , Microdominios de Membrana/metabolismo , ARN Interferente Pequeño/metabolismo , ARN Mensajero/metabolismo
13.
Ann Vasc Surg ; 88: 218-227, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36058458

RESUMEN

BACKGROUND: The recommendation of the European Society for Vascular Surgery (ESVS) is that vertebral revascularization combined with ipsilateral CEA (carotid endarterectomy) should not be performed in the same operation. ESVS believes that vertebral revascularization combined with ipsilateral CEA increases perioperative death/stroke rates. In our opinion, revascularization of the first segment of vertebral artery (V1) combined with ipsilateral CEA is safe compared to vertebral V1 revascularization in the perioperative period. The purpose of this study is to prove that revascularization of V1 segment of vertebral artery combined with ipsilateral CEA is secure in the perioperative period. METHODS: We describe our experience with homochronous revascularization of V1 segment of vertebral artery with ipsilateral CEA (group B) and simple revascularization of V1 segment of vertebral artery (group A) in 48 consecutive patients during a 5-year period. O.Y. (Ouyang) incisions were used in both groups. We compare the results of the 2 procedures with aspects of mortality, stroke, morbidity, incident rates of complications, and so on. RESULTS: There was no significant difference between patients in group A and group B in terms of red blood cell reduction, postoperative ventilator using time, postoperative drainage volume, postoperative drainage days, postoperative hospitalize duration, and incident rates of postoperative complications. The postoperative complications include death, stroke, Horner syndrome, vocal paralysis, hypoglossal nerve paralysis, wound hematomas, and lymphatic leakage. CONCLUSIONS: Revascularization of vertebral artery combined with ipsilateral CEA should be divided into revascularization of V1 segment of vertebral artery combined with ipsilateral CEA and revascularization of V3 segment of vertebral artery with ipsilateral CEA. Revascularization of V1 segment of vertebral artery combined with ipsilateral CEA is safe; it can be performed for suitable patients who are fit for indications. O.Y. incisions can fully expose the target blood vessels and simplify the procedures without transecting the sternocleidomastoid muscles in operations.


Asunto(s)
Estenosis Carotídea , Endarterectomía Carotidea , Accidente Cerebrovascular , Humanos , Endarterectomía Carotidea/efectos adversos , Estenosis Carotídea/complicaciones , Estenosis Carotídea/diagnóstico por imagen , Estenosis Carotídea/cirugía , Arteria Vertebral/diagnóstico por imagen , Arteria Vertebral/cirugía , Stents/efectos adversos , Resultado del Tratamiento , Estudios Retrospectivos , Factores de Tiempo , Accidente Cerebrovascular/etiología , Complicaciones Posoperatorias , Parálisis
14.
Iran J Public Health ; 51(8): 1778-1789, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36249115

RESUMEN

Background: Clinical investigations repurposing a disintegrin and metalloproteases 10 (ADAM10) as metastatic and thrombus marker have achieved encouraging results, but the mechanism behind this association remains unclear. Methods: This study was carried out in NingXia and Wuhan, China from 2017 to 2021. The effects of ADAM10 expression on the metastatic and thrombus-associated genes: tissue factor (TF), P-selectin glycoprotein ligand-1 (PSGL-1), cathepsin G (CTSG) and mucin 1 (MUC1) were examined by immunofluorescence, qRTPCR and Western blotting analysis. Metastatic and thrombotic behaviors were evaluated using NODSCID mouse model. Results: The ADAM10 expression controlled the migration and invasion of pancreatic carcinoma cell-1(PANC-1), and significantly regulated the metastatic and thrombus-associated genes (P<0.05). ADAM10 and MUC1 were regulated and aberrantly expressed by a dependent mechanism. Moreover, ADAM10 expression induced the progression of adenocarcinoma cells and thrombus formation in vivo. Conclusion: Regulation of ADAM10 expression in cancer cells might effectively pave the way for a more potent anti-metastatic and anti-thrombotic approach and could regulate the invasion and migration of cancer cells.

15.
Int J Biol Sci ; 18(7): 2655-2669, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35541916

RESUMEN

SIRT1 (silent mating type information regulation 2 homolog 1), a class III histone deacetylase, is known to participate in multiple steps of the DNA damage response (DDR) by deacetylating several key DDR proteins. At present, the mechanisms regulating SIRT1 protein stability upon DNA damage have yet to be fully elucidated. In this study, we reveal that, under severe DNA damage, SIRT1 undergoes two forms of post-translational modifications (PTMs): (i) increased polyubiquitination and proteasomal degradation mediated by TRIM28 (tripartite motif-containing protein 28), a RING-domain E3 ligase; and (ii) cleavage at C-terminal mediated by caspases. Importantly, there is reciprocal effects between these forms of PTMs: while suppression of proteasome reduces caspases-mediated cleavage, the cleaved SIRT1 has enhanced interaction with TRIM28, thus facilitating the ubiquitination and proteasomal degradation of SIRT1. Functionally, SIRT1 works as an anti-apoptotic protein in DDR, and the above-mentioned PTMs of SIRT1 subsequently enhances cell death induced by DNA damage agents. Thus, our study has uncovered a pivotal role of SIRT1 post-translational regulation in determining cell fate in DDR.


Asunto(s)
Procesamiento Proteico-Postraduccional , Sirtuina 1 , Caspasas/genética , Daño del ADN/genética , Procesamiento Proteico-Postraduccional/genética , Sirtuina 1/genética , Sirtuina 1/metabolismo , Factores de Transcripción/metabolismo , Ubiquitinación
16.
Autophagy ; 18(10): 2270-2287, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35090378

RESUMEN

Vascular smooth muscle cells (VSMCs) contribute to plaque stability. VSMCs are also a major source of CTH (cystathionine gamma-lyase)-hydrogen sulfide (H2S), a protective gasotransmitter in atherosclerosis. However, the role of VSMC endogenous CTH-H2S in pathogenesis of plaque stability and the mechanism are unknown. In human carotid plaques, CTH expression in ACTA2+ cells was dramatically downregulated in lesion areas in comparison to non-lesion areas. Intraplaque CTH expression was positively correlated with collagen content, whereas there was a negative correlation with CD68+ and necrotic core area, resulting in a rigorous correlation with vulnerability index (r = -0.9033). Deletion of Cth in VSMCs exacerbated plaque vulnerability, and were associated with VSMC autophagy decline, all of which were rescued by H2S donor. In ox-LDL treated VSMCs, cth deletion reduced collagen and heightened apoptosis association with autophagy reduction, and vice versa. For the mechanism, CTH-H2S mediated VSMC autophagosome formation, autolysosome formation and lysosome function, in part by activation of TFEB, a master regulator for autophagy. Interference with TFEB blocked CTH-H2S effects on VSMCs collagen and apoptosis. Next, we demonstrated that CTH-H2S sulfhydrated TFEB at Cys212 site, facilitating its nuclear translocation, and then promoting transcription of its target genes such as ATG9A, LAPTM5 or LDLRAP1. Conclusively, CTH-H2S increases VSMC autophagy by sulfhydration and activation of TFEB, promotes collagen secretion and inhibits apoptosis, thereby attenuating atherogenesis and plaque vulnerability. CTH-H2S may act as a warning biomarker for vulnerable plaque.Abbreviations ATG9A: autophagy related 9A; CTH: cystathionine gamma-lyase; CQ: chloroquine; HASMCs: human aortic smooth muscle cells; H2S: hydrogen sulfide; LAMP1: lysosomal associated membrane protein 1; LAPTM5: lysosomal protein transmembrane 5; NaHS: sodium hydrosulfide hydrate; ox-LDL: oxidized-low density lipoprotein; PPG: DL- propagylglycine; TFEB: transcription factor EB; 3-MA: 3-methyladenine; VSMCs: vascular smooth muscle cells.


Asunto(s)
Aterosclerosis , Gasotransmisores , Sulfuro de Hidrógeno , Placa Aterosclerótica , Aterosclerosis/patología , Autofagia , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/metabolismo , Biomarcadores/metabolismo , Cloroquina , Cistationina gamma-Liasa/genética , Cistationina gamma-Liasa/metabolismo , Gasotransmisores/metabolismo , Humanos , Sulfuro de Hidrógeno/metabolismo , Sulfuro de Hidrógeno/farmacología , Lipoproteínas LDL/metabolismo , Proteína 1 de la Membrana Asociada a los Lisosomas/metabolismo , Músculo Liso Vascular/patología , Miocitos del Músculo Liso/metabolismo , Placa Aterosclerótica/patología
17.
J Empir Res Hum Res Ethics ; 17(3): 362-372, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35088620

RESUMEN

This study aims to investigate the knowledge and attitudes of participants and potential participants in clinical trials toward electronic informed consent. We conducted a survey-based cross-sectional study in Hunan Province, China in March 2021. A total of 547 respondents were included in this study. All questions in an 8-item survey section assessing participants' knowledge of electronic informed consent received correct answers from at least 70% of participants. In terms of attitude scores, most participants (86.3%) believed that electronic informed consent is more convenient than the paper-based version, and more than half (51.2%) believed that electronic informed consent could completely replace the paper-based version. Responses indicated that common concerns about electronic informed consent were its security and confidentiality, legal benefits, and implications for rights protection.


Asunto(s)
Electrónica , Consentimiento Informado , Actitud , Estudios Transversales , Humanos , Encuestas y Cuestionarios
18.
J Biomater Appl ; 36(6): 965-975, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34284662

RESUMEN

BACKGROUND: The most common materials of artificial blood vessels are polyethylene terephthalate and polytetrafluoroethylene. But polycarbonate polyurethane (PCU) is an ideal material for vascular prostheses because of their excellent characteristics. As far as we know, our artificial blood vessel is the first type of hybrid PCU/polyester three-layered large-diameter artificial blood vessel in the world. OBJECTIVE: The purpose of this preclinical animal experiment is to evaluate the hemocompatibility, histocompatibility, effectiveness, and safety of the three-layered large-diameter artificial blood vessel in sheep. METHODS: The artificial blood vessels took place of the initial segments of the sheep's thoracic aorta by end-to-end anastomosis. RESULTS: All of the 14 sheep are male, their average body weight (BW) was 30.57 ± 3.95 kg. All 14 artificial blood vessels successfully replaced the thoracic aortas. 5 sheep did not survive to the end of the experiment, while the remaining 9 sheep did. After the surgery, the blood biochemical and blood routine indicators fluctuate slightly within the normal range. The angiography showed that the implanted artificial blood vessels were unobstructed without obvious stenosis or expansion. 24 weeks after surgery, the lumen surfaces of the artificial blood vessels were covered by endothelia in different degrees, and the average endothelialization rate was 69.44% (range: 20% to 100%). CONCLUSIONS: This artificial blood vessel is the first to use PCU in large-diameter artificial vascular grafts. It has excellent blood compatibility, wonderful biocompatibility, high endothelialization rate, and 100% patency.


Asunto(s)
Sustitutos Sanguíneos , Poliuretanos , Animales , Prótesis Vascular , Masculino , Cemento de Policarboxilato , Poliésteres , Politetrafluoroetileno , Ovinos
19.
Colloids Surf B Biointerfaces ; 205: 111894, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34118532

RESUMEN

Effective surface modification to endow pyrolytic carbon (PYC) with long-term anti-thrombotic performance is highly demanded. In this work, a gradient hydrophobic surface on PYC was prepared by creating parallel ridges via the combination of laser etching technology and surface fluorosilanization. Scanning electron microscopy (SEM) observation confirms that the gradient hydrophobic surface is composed of a bare PYC region and four regions of parallel ridges with varying distances. The gradient hydrophobic surface is stable in air, phosphate buffer solution (PBS), and flowing PBS. Additionally, the gradient hydrophobic surface on PYC shows spontaneous droplet motion and much lower flow resistance than bare PYC. Compared to bare PYC, the gradient hydrophobic surface on PYC exhibits better blood compatibility and anti-adhesion performance. The results presented in this paper confirm that creating a gradient hydrophobic surface is an effective way of achieving long-lasting anti-thrombosis property.


Asunto(s)
Prótesis Valvulares Cardíacas , Corazón Artificial , Carbono , Interacciones Hidrofóbicas e Hidrofílicas
20.
Ann Vasc Surg ; 75: 294-300, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-33819595

RESUMEN

OBJECTIVE: Isolated true subclavian artery aneurysm (SAA) without aberrant subclavian artery or coarctation of descending aorta is a rare peripheral aneurysm. Herein, the experience of our medical center in the treatment of this disease is presented. METHODS: The Division operative log was queried to identify cases of SAA repair between January 2012 and September 2019 that were not associated with coarctation of the aorta or the presence of an aberrant subclavian artery. A total of 22 cases were identified. The characteristics, treatment and clinical outcomes of these cases were assessed. RESULTS: The mean age of patients was 53.5 ± 14.3 years and 14 patients were male (63.6%). Half of the cases were attributed to atherosclerotic degeneration. The clinical symptoms of aneurysms were varied, including asymptomatic, pulsatile mass of supraclavicular fossa, local pain, upper limb embolism, Horner's syndrome and hoarseness. Aneurysms were located on the right in 17 cases, on the left in 3 cases and on both sides in 2 cases. Fifteen (68%) patients underwent an intervention, of which 11 (50%) underwent an open surgical repair, and 4 (18%) underwent endovascular repair. The mean diameter of the aneurysms was 39.5 ± 20.7 mm in the open surgery group, and 24.0 ± 4.7 mm in the endovascular group. The follow-up duration ranged from 2 months to 12 years. One patient died of cardiogenic disease in the untreated group. Patients undergoing open operative repair had 100% patency of the reconstruction. In the endovascular group, one patient had stent occlusion 2 years after the operation. CONCLUSIONS: The most common cause of isolated subclavian aneurysm without aberrant subclavian artery or coarctation of descending aorta is atherosclerosis. The clinical symptoms of aneurysms are varied, and the aneurysms tend to occur on the right side. Based on the anatomical conditions of SAAs, open surgery and endovascular repair can be used for treatment.


Asunto(s)
Aneurisma/cirugía , Procedimientos Endovasculares , Arteria Subclavia/cirugía , Procedimientos Quirúrgicos Vasculares , Adulto , Anciano , Aneurisma/diagnóstico por imagen , Aneurisma/etiología , Aterosclerosis/complicaciones , Bases de Datos Factuales , Procedimientos Endovasculares/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Arteria Subclavia/diagnóstico por imagen , Factores de Tiempo , Resultado del Tratamiento , Procedimientos Quirúrgicos Vasculares/efectos adversos
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