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1.
Cell Mol Life Sci ; 81(1): 224, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38769196

RESUMO

Synaptic loss is an early event in the penumbra area after an ischemic stroke. Promoting synaptic preservation in this area would likely improve functional neurological recovery. We aimed to detect proteins involved in endogenous protection mechanisms of synapses in the penumbra after stroke and to analyse potential beneficial effects of these candidates for a prospective stroke treatment. For this, we performed Liquid Chromatography coupled to Mass Spectrometry (LC-MS)-based proteomics of synaptosomes isolated from the ipsilateral hemispheres of mice subjected to experimental stroke at different time points (24 h, 4 and 7 days) and compared them to sham-operated mice. Proteomic analyses indicated that, among the differentially expressed proteins between the two groups, cystatin C (CysC) was significantly increased at 24 h and 4 days following stroke, before returning to steady-state levels at 7 days, thus indicating a potential transient and intrinsic rescue mechanism attempt of neurons. When CysC was applied to primary neuronal cultures subjected to an in vitro model of ischemic damage, this treatment significantly improved the preservation of synaptic structures. Notably, similar effects were observed when CysC was loaded into brain-derived extracellular vesicles (BDEVs). Finally, when CysC contained in BDEVs was administered intracerebroventricularly to stroked mice, it significantly increased the expression of synaptic markers such as SNAP25, Homer-1, and NCAM in the penumbra area compared to the group supplied with empty BDEVs. Thus, we show that CysC-loaded BDEVs promote synaptic protection after ischemic damage in vitro and in vivo, opening the possibility of a therapeutic use in stroke patients.


Assuntos
Isquemia Encefálica , Encéfalo , Cistatina C , Vesículas Extracelulares , Camundongos Endogâmicos C57BL , Sinapses , Animais , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/transplante , Cistatina C/metabolismo , Sinapses/metabolismo , Camundongos , Masculino , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Encéfalo/metabolismo , Encéfalo/patologia , Proteômica/métodos , Sinaptossomos/metabolismo , Neurônios/metabolismo , Acidente Vascular Cerebral/metabolismo , Acidente Vascular Cerebral/patologia , Acidente Vascular Cerebral/terapia , Células Cultivadas , Modelos Animais de Doenças
2.
Int J Esthet Dent ; 19(2): 126-138, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38726855

RESUMO

AIM: The aim of the present retrospective case series was to longitudinally assess soft tissue volume changes on the vestibular aspect of implants in relation to keratinized mucosa thickness (KMT) and width (KMW) after the application of the microsurgical envelope technique combined with a connective tissue graft (CTG). MATERIALS AND METHODS: A total of 12 healthy patients received 12 dental implants placed either in the posterior maxilla or mandible. The study involved the harvesting of 12 CTGs with a minimally invasive single-incision technique, grafted to the vestibular peri-implant soft tissue utilizing the envelope technique, followed by the insertion of 12 screw-retained IPS e.max crowns. RESULTS: The healing process was uneventful across all areas, and all patients were followed up for a period of 5 years. The evaluation of KMT showed the highest decrease in the first 6 weeks after surgery (5.5 ± 0.79 to 4.59 ± 0.62 mm), then dropped slightly to 4 ± 0.85 mm, after which it maintained at 4 ± 0.36 mm until the 2-year time point. Between the second and third years after surgery, a further decrease of 3.59 ± 0.42 mm was recorded for KMT, which then remained constant until the end of the 5-year research period. The observations regarding KMW were slightly different, with the measurements demonstrating the greatest decrease in first 6 weeks (from 2.5 ± 0.42 to 1.5 ± 0.42 mm), which was maintained until the 1-year time point. Between the first and second years after surgery, the KMW increased to 2 ± 0.60 mm and remained level for the next 3 years, at 2 ± 0.85 mm. CONCLUSIONS: The current research demonstrated the advantages of using a combination of a minimally invasively harvested CTG and the microsurgical envelope technique for a duration of 5 years.


Assuntos
Tecido Conjuntivo , Microcirurgia , Humanos , Estudos Retrospectivos , Tecido Conjuntivo/transplante , Masculino , Microcirurgia/métodos , Feminino , Adulto , Pessoa de Meia-Idade , Implantação Dentária Endóssea/métodos , Implantes Dentários , Maxila/cirurgia , Mandíbula/cirurgia , Gengiva/transplante
3.
Front Immunol ; 15: 1409021, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38751430

RESUMO

Chimeric antigen receptor-T (CAR-T) cell therapy has made remarkable strides in treating hematological malignancies. However, the widespread adoption of CAR-T cell therapy is hindered by several challenges. These include concerns about the long-term and complex manufacturing process, as well as efficacy factors such as tumor antigen escape, CAR-T cell exhaustion, and the immunosuppressive tumor microenvironment. Additionally, safety issues like the risk of secondary cancers post-treatment, on-target off-tumor toxicity, and immune effector responses triggered by CAR-T cells are significant considerations. To address these obstacles, researchers have explored various strategies, including allogeneic universal CAR-T cell development, infusion of non-activated quiescent T cells within a 24-hour period, and in vivo induction of CAR-T cells. This review comprehensively examines the clinical challenges of CAR-T cell therapy and outlines strategies to overcome them, aiming to chart pathways beyond its current Achilles heels.


Assuntos
Imunoterapia Adotiva , Receptores de Antígenos Quiméricos , Linfócitos T , Humanos , Imunoterapia Adotiva/métodos , Imunoterapia Adotiva/efeitos adversos , Receptores de Antígenos Quiméricos/imunologia , Receptores de Antígenos Quiméricos/genética , Animais , Linfócitos T/imunologia , Linfócitos T/transplante , Microambiente Tumoral/imunologia , Neoplasias Hematológicas/terapia , Neoplasias Hematológicas/imunologia , Antígenos de Neoplasias/imunologia , Receptores de Antígenos de Linfócitos T/imunologia
4.
Bull Hosp Jt Dis (2013) ; 82(2): 118-123, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38739659

RESUMO

OBJECTIVE: The purpose of this study was to compare the short-term clinical outcomes of matrix-induced autologous chondrocyte implantation (MACI) to those seen following traditional autologous chondrocyte implantation (ACI) in the management of symptomatic cartilage lesions of the knee. METHODS: This was a retrospective cohort study of patients who underwent either ACI or MACI from January 2011 to March 2018. Patients with a minimum postoperative follow-up of 18 months were contacted. Demographic information, intraoperative findings, and patient-reported functional outcomes scores were collected. Comparisons were made between the two cell-based cartilage repair techniques. RESULTS: Fifty-six patients were included in the study (39 ACI, 17 MACI). Visual analog scale (VAS) for pain scores improved significantly in both groups, with MACI patients demonstrating significantly lower postoperative pain scores compared to those treated with ACI. In the ACI group, there was a decrease in the Tegner Activity score compared to the preoperative baseline, while no significant difference was seen between pre- and postoperative activity levels in the MACI group. Patients were generally satisfied with the outcome of their procedures, and there was no significant difference in satisfaction between groups. No patients re-quired additional surgery during the follow-up period. CONCLUSION: Both ACI and MACI demonstrated good short-term postoperative clinical results with improved pain and activity levels compared to the preoperative baseline. Patients treated with the MACI technique demonstrated greater reductions in pain scores compared to ACI, and while ACI resulted in a decrease in levels of postoperative activity, activity levels for MACI remained stable.


Assuntos
Condrócitos , Articulação do Joelho , Transplante Autólogo , Humanos , Condrócitos/transplante , Estudos Retrospectivos , Feminino , Masculino , Adulto , Resultado do Tratamento , Articulação do Joelho/cirurgia , Articulação do Joelho/fisiopatologia , Pessoa de Meia-Idade , Cartilagem Articular/cirurgia , Medição da Dor , Satisfação do Paciente , Adulto Jovem
5.
Function (Oxf) ; 5(3): zqae012, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38706963

RESUMO

Acute kidney injury (AKI) is a heterogeneous syndrome, comprising diverse etiologies of kidney insults that result in high mortality and morbidity if not well managed. Although great efforts have been made to investigate underlying pathogenic mechanisms of AKI, there are limited therapeutic strategies available. Extracellular vesicles (EV) are membrane-bound vesicles secreted by various cell types, which can serve as cell-free therapy through transfer of bioactive molecules. In this review, we first overview the AKI syndrome and EV biology, with a particular focus on the technical aspects and therapeutic application of cell culture-derived EVs. Second, we illustrate how multi-omic approaches to EV miRNA, protein, and genomic cargo analysis can yield new insights into their mechanisms of action and address unresolved questions in the field. We then summarize major experimental evidence regarding the therapeutic potential of EVs in AKI, which we subdivide into stem cell and non-stem cell-derived EVs. Finally, we highlight the challenges and opportunities related to the clinical translation of animal studies into human patients.


Assuntos
Injúria Renal Aguda , Vesículas Extracelulares , Injúria Renal Aguda/terapia , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/patologia , Humanos , Vesículas Extracelulares/transplante , Vesículas Extracelulares/metabolismo , Animais , Técnicas de Cultura de Células/métodos , MicroRNAs/metabolismo , MicroRNAs/genética
6.
Artigo em Inglês | MEDLINE | ID: mdl-38712707

RESUMO

In a 39-year-old male with mitral valve endocarditis, after 6 weeks of intravenous antibiotics, echocardiography confirmed multiple vegetations on both leaflets, a flail posterior leaflet flail and contained perforation of the anterior leaflet in a windsock-like morphology. All vegetations, diseased and ruptured chords and the windsock-like contained rupture of the anterior leaflet were carefully resected via a right minithoracotomy and with femoral cannulation. Three repair techniques were blended to reconstruct the valve: (1) A large, infected portion of the prolapsing posterior leaflet was resected in a triangular fashion, and the edges were re-approximated using continuous 5-0 polypropylene sutures. (2) The anterior leaflet defect was repaired with a circular autologous pericardial patch that had been soaked in glutaraldehyde. (3) A set of artificial chords for P2 was created using CV-4 polytetrafluoroethylene sutures and adjusted under repeated saline inflation. A 38-mm Edwards Physio-I annuloplasty ring was implanted. The artificial chords were adjusted again after annuloplasty and then tied. Transoesophageal echocardiography (TEE) confirmed the absence of residual mitral regurgitation and systolic anterior motion and a mean pressure gradient of 3 mmHg. The patient was discharged after 5 days with a peripherally inserted central catheter to complete an additional 4 weeks of intravenous antibiotics and had an uneventful recovery.


Assuntos
Ecocardiografia Transesofagiana , Valva Mitral , Humanos , Masculino , Adulto , Valva Mitral/cirurgia , Anuloplastia da Valva Mitral/métodos , Endocardite Bacteriana/cirurgia , Endocardite Bacteriana/diagnóstico , Insuficiência da Valva Mitral/cirurgia , Insuficiência da Valva Mitral/diagnóstico , Técnicas de Sutura , Implante de Prótese de Valva Cardíaca/métodos , Endocardite/cirurgia , Endocardite/diagnóstico , Pericárdio/transplante
7.
BMJ Case Rep ; 17(5)2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38749513

RESUMO

We present two cases which underwent complex ocular surface reconstruction to achieve a stable ocular surface. Conjunctival autograft (CAG) procedure was required more than once, in addition to simple limbal epithelial transplantation to address extensive symblepharon in the eyes with total unilateral limbal stem cell deficiency secondary to acid ocular burns. These cases demonstrate that multiple CAGs may be harvested from the contralateral unaffected eye to correct recurrent symblepharon without any donor site complications if the correct surgical technique is adopted.


Assuntos
Autoenxertos , Queimaduras Químicas , Túnica Conjuntiva , Queimaduras Oculares , Humanos , Queimaduras Químicas/cirurgia , Queimaduras Oculares/cirurgia , Queimaduras Oculares/induzido quimicamente , Túnica Conjuntiva/transplante , Masculino , Adulto , Feminino , Transplante Autólogo , Doenças da Túnica Conjuntiva/cirurgia , Limbo da Córnea/cirurgia , Recidiva
8.
Artigo em Inglês | MEDLINE | ID: mdl-38749719

RESUMO

An 82-year-old male patient underwent a left upper lobectomy with anterolateral thoracotomy for lung cancer. Although a complete left-pericardial defect was observed during surgery, the pericardial repair was not performed because the left lower lobe remained and the heart was considered stable. Postoperative pathological examination revealed primary synchronous double-lung squamous-cell carcinoma (pathological stage pT2a(2)N0M0 stage IB). He was discharged without complications on postoperative day 8. Leftward displacement of the heart and left diaphragmatic elevation, suspected of phrenic-nerve paralysis, were found in the chest X-ray after discharge. However, the patient's overall condition remained unaffected at the 5-month postoperative follow-up. To assess the need for pericardial repair, we compared cases of complete pericardial defects observed during lobectomy or pneumonectomy reported in the literature. Only one of 12 cases occurred postoperative death despite pericardial repair, and that case combined pectus excavatum and pericardial defects. Our assessment indicated that pericardial repair might not be necessary, excluding complex cases.


Assuntos
Carcinoma de Células Escamosas , Achados Incidentais , Neoplasias Pulmonares , Pericárdio , Pneumonectomia , Humanos , Masculino , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Pneumonectomia/efeitos adversos , Pericárdio/transplante , Idoso de 80 Anos ou mais , Resultado do Tratamento , Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/patologia , Toracotomia , Tomografia Computadorizada por Raios X , Cardiopatias Congênitas/cirurgia , Cardiopatias Congênitas/diagnóstico por imagem , Estadiamento de Neoplasias
9.
Clin Oral Investig ; 28(6): 317, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38750335

RESUMO

OBJECTIVES: To evaluate the effects of costochondral grafting (CCG) used for temporomandibular joint ankylosis (TMJA) in growing patients. MATERIALS AND METHODS: Pediatric patients with TMJA treated by CCG from 2010.5 to 2021.7 were included in the study. CT scans were performed before and after operations with at least 1 year follow-up. The height of the mandibular ramus, menton deviation or retraction, osteotomy gap, etc. were measured by ProPlan CMF1.4 software. CCG growth, resorption, and relapse were evaluated and analyzed with influencing factors such as age, ostectomy gap, etc. by generalized estimating equation. RESULTS: There were 24 patients (29 joints) with an average age of 6.30 ± 3.13 years in the study. After operation, the mandibular ramus was elongated by 5.97 ± 3.53 mm. Mandibular deviation or retrusion was corrected by 4.82 ± 2.84 mm and 3.76 ± 2.97 mm respectively. After a mean follow-up of 38.91 ± 29.20 months, 58.62% CCG grew (4.18 ± 7.70 mm), 20.69% absorbed (2.23 ± 1.16 mm), and 20.69% re-ankylosed. The re-ankylosis was negatively correlated with the osteotomy gap (OR:0.348,0.172-0.702 95%CI, critical value = 6.10 mm). CCG resorption was positively correlated with the distance of CCG ramus elongation (OR:3.353,1.173-9.586 95%CI, critical value = 7.40 mm). CONCLUSIONS: An adequate osteotomy gap and CCG ramus elongation distance are the key factors for successful treatment of TMJA with jaw deformities in growing patients. CLINICAL RELEVANCE: TMJA affects mouth opening and jaw development in pediatric patients. The most common autogenous bone graft for pediatric patients is CCG due to its growth potential, convenient access and easy contouring. Also, it can simultaneously reconstruct the TMJ and improve jaw deformity by lengthening the mandibular ramus. But the growth of CCG is unpredictable. In this study, we explored several factors that may affect the absorption and re-ankylosis of CCG, expecting to provide several suggestions to improve future CCG treatment.


Assuntos
Anquilose , Transtornos da Articulação Temporomandibular , Tomografia Computadorizada por Raios X , Humanos , Criança , Transtornos da Articulação Temporomandibular/cirurgia , Transtornos da Articulação Temporomandibular/diagnóstico por imagem , Feminino , Anquilose/cirurgia , Masculino , Resultado do Tratamento , Costelas/transplante , Transplante Ósseo/métodos , Pré-Escolar , Estudos Retrospectivos , Cartilagem/transplante
10.
Front Immunol ; 15: 1385022, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38694507

RESUMO

Liver failure represents a critical medical condition with a traditionally grim prognosis, where treatment options have been notably limited. Historically, liver transplantation has stood as the sole definitive cure, yet the stark disparity between the limited availability of liver donations and the high demand for such organs has significantly hampered its feasibility. This discrepancy has necessitated the exploration of hepatocyte transplantation as a temporary, supportive intervention. In light of this, our review delves into the burgeoning field of hepatocyte transplantation, with a focus on the latest advancements in maintaining hepatocyte function, co-microencapsulation techniques, xenogeneic hepatocyte transplantation, and the selection of materials for microencapsulation. Our examination of hepatocyte microencapsulation research highlights that, to date, most studies have been conducted in vitro or using liver failure mouse models, with a notable paucity of experiments on larger mammals. The functionality of microencapsulated hepatocytes is primarily inferred through indirect measures such as urea and albumin production and the rate of ammonia clearance. Furthermore, research on the mechanisms underlying hepatocyte co-microencapsulation remains limited, and the practicality of xenogeneic hepatocyte transplantation requires further validation. The potential of hepatocyte microencapsulation extends beyond the current scope of application, suggesting a promising horizon for liver failure treatment modalities. Innovations in encapsulation materials and techniques aim to enhance cell viability and function, indicating a need for comprehensive studies that bridge the gap between small-scale laboratory success and clinical applicability. Moreover, the integration of bioengineering and regenerative medicine offers novel pathways to refine hepatocyte transplantation, potentially overcoming the challenges of immune rejection and ensuring the long-term functionality of transplanted cells. In conclusion, while hepatocyte microencapsulation and transplantation herald a new era in liver failure therapy, significant strides must be made to translate these experimental approaches into viable clinical solutions. Future research should aim to expand the experimental models to include larger mammals, thereby providing a clearer understanding of the clinical potential of these therapies. Additionally, a deeper exploration into the mechanisms of cell survival and function within microcapsules, alongside the development of innovative encapsulation materials, will be critical in advancing the field and offering new hope to patients with liver failure.


Assuntos
Encapsulamento de Células , Sobrevivência Celular , Hepatócitos , Animais , Humanos , Encapsulamento de Células/métodos , Hepatócitos/transplante , Hepatócitos/citologia , Falência Hepática/terapia , Transplante Heterólogo
11.
Front Immunol ; 15: 1390498, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38694508

RESUMO

Recent advancements in genetic engineering have made it possible to modify Natural Killer (NK) cells to enhance their ability to fight against various cancers, including solid tumors. This comprehensive overview discusses the current status of genetically engineered chimeric antigen receptor NK-cell therapies and their potential for treating solid tumors. We explore the inherent characteristics of NK cells and their role in immune regulation and tumor surveillance. Moreover, we examine the strategies used to genetically engineer NK cells in terms of efficacy, safety profile, and potential clinical applications. Our investigation suggests CAR-NK cells can effectively target and regress non-hematological malignancies, demonstrating enhanced antitumor efficacy. This implies excellent promise for treating tumors using genetically modified NK cells. Notably, NK cells exhibit low graft versus host disease (GvHD) potential and rarely induce significant toxicities, making them an ideal platform for CAR engineering. The adoptive transfer of allogeneic NK cells into patients further emphasizes the versatility of NK cells for various applications. We also address challenges and limitations associated with the clinical translation of genetically engineered NK-cell therapies, such as off-target effects, immune escape mechanisms, and manufacturing scalability. We provide strategies to overcome these obstacles through combination therapies and delivery optimization. Overall, we believe this review contributes to advancing NK-cell-based immunotherapy as a promising approach for cancer treatment by elucidating the underlying mechanisms, evaluating preclinical and clinical evidence, and addressing remaining challenges.


Assuntos
Engenharia Genética , Imunoterapia Adotiva , Células Matadoras Naturais , Neoplasias , Receptores de Antígenos Quiméricos , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/transplante , Humanos , Neoplasias/terapia , Neoplasias/imunologia , Imunoterapia Adotiva/métodos , Receptores de Antígenos Quiméricos/genética , Receptores de Antígenos Quiméricos/imunologia , Animais
12.
J Extracell Vesicles ; 13(5): e12433, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38738585

RESUMO

Extracellular vesicles (EVs) are released by all cells and contribute to cell-to-cell communication. The capacity of EVs to target specific cells and to efficiently deliver a composite profile of functional molecules have led researchers around the world to hypothesize their potential as therapeutics. While studies of EV treatment in animal models are numerous, their actual clinical benefit in humans has more slowly started to be tested. In this scoping review, we searched PubMed and other databases up to 31 December 2023 and, starting from 13,567 records, we selected 40 pertinent published studies testing EVs as therapeutics in humans. The analysis of those 40 studies shows that they are all small pilot trials with a large heterogeneity in terms of administration route and target disease. Moreover, the absence of a placebo control in most of the studies, the predominant local application of EV formulations and the inconsistent administration dose metric still impede comparison across studies and firm conclusions about EV safety and efficacy. On the other hand, the recording of some promising outcomes strongly calls out for well-designed larger studies to test EVs as an alternative approach to treat human diseases with no or few therapeutic options.


Assuntos
Vesículas Extracelulares , Animais , Humanos , Comunicação Celular , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/transplante
14.
J Hematol Oncol ; 17(1): 29, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38711046

RESUMO

Currently, many off-the-shelf chimeric antigen receptor (CAR)-T cell products are under investigation for the treatment of relapsed or refractory (R/R) B-cell neoplasms. Compared with autologous CAR-T cell therapy, off-the-shelf universal CAR-T cell therapies have many potential benefits, such as immediate accessibility for patients, stable quality due to industrialized manufacturing and additional infusions of CAR-T cells with different targets. However, critical challenges, including graft-versus-host disease and CAR-T cell elimination by the host immune system, still require extensive research. The most common technological approaches involve modifying healthy donor T cells via gene editing technology and altering different types of T cells. This article summarizes some of the latest data from preclinical and clinical studies of off-the-shelf CAR-T cell therapies in the treatment of R/R B-cell malignancies from the 2023 ASH Annual Meeting (ASH 2023).


Assuntos
Imunoterapia Adotiva , Receptores de Antígenos Quiméricos , Humanos , Imunoterapia Adotiva/métodos , Receptores de Antígenos Quiméricos/imunologia , Receptores de Antígenos Quiméricos/uso terapêutico , Leucemia de Células B/terapia , Leucemia de Células B/imunologia , Linfoma de Células B/terapia , Linfoma de Células B/imunologia , Linfócitos T/imunologia , Linfócitos T/transplante
15.
J Extracell Vesicles ; 13(5): e12445, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38711334

RESUMO

Small extracellular vesicles (sEV) derived from various cell sources have been demonstrated to enhance cardiac function in preclinical models of myocardial infarction (MI). The aim of this study was to compare different sources of sEV for cardiac repair and determine the most effective one, which nowadays remains limited. We comprehensively assessed the efficacy of sEV obtained from human primary bone marrow mesenchymal stromal cells (BM-MSC), human immortalized MSC (hTERT-MSC), human embryonic stem cells (ESC), ESC-derived cardiac progenitor cells (CPC), human ESC-derived cardiomyocytes (CM), and human primary ventricular cardiac fibroblasts (VCF), in in vitro models of cardiac repair. ESC-derived sEV (ESC-sEV) exhibited the best pro-angiogenic and anti-fibrotic effects in vitro. Then, we evaluated the functionality of the sEV with the most promising performances in vitro, in a murine model of MI-reperfusion injury (IRI) and analysed their RNA and protein compositions. In vivo, ESC-sEV provided the most favourable outcome after MI by reducing adverse cardiac remodelling through down-regulating fibrosis and increasing angiogenesis. Furthermore, transcriptomic, and proteomic characterizations of sEV derived from hTERT-MSC, ESC, and CPC revealed factors in ESC-sEV that potentially drove the observed functions. In conclusion, ESC-sEV holds great promise as a cell-free treatment for promoting cardiac repair following MI.


Assuntos
Vesículas Extracelulares , Células-Tronco Mesenquimais , Infarto do Miocárdio , Miócitos Cardíacos , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/transplante , Humanos , Animais , Camundongos , Infarto do Miocárdio/terapia , Infarto do Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/citologia , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia , Células-Tronco Embrionárias/metabolismo , Células-Tronco Embrionárias/citologia , Células-Tronco Embrionárias Humanas/citologia , Células-Tronco Embrionárias Humanas/metabolismo , Fibroblastos/metabolismo , Masculino , Traumatismo por Reperfusão Miocárdica/terapia , Traumatismo por Reperfusão Miocárdica/metabolismo , Modelos Animais de Doenças , Neovascularização Fisiológica , Células Cultivadas
16.
Tex Heart Inst J ; 51(1)2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38711341

RESUMO

A 62-year-old woman who had undergone mitral valve replacement 24 years ago was admitted to the hospital with congestive heart failure. She needed heart transplantation for stage D heart failure. Preoperative cardiac computed tomographic scans showed a severely calcified left atrium and a large right atrium. Given that the left atrium's calcification was too severe to suture, the calcified left atrial wall was broadly resected, and the resected left atrial wall was reconstructed with a bovine pericardial patch for anastomosis with the donor's left atrial wall. The operation was completed without heavy bleeding, and the patient was discharged from the hospital with no complications.


Assuntos
Calcinose , Átrios do Coração , Insuficiência Cardíaca , Transplante de Coração , Cardiopatia Reumática , Tomografia Computadorizada por Raios X , Humanos , Feminino , Cardiopatia Reumática/cirurgia , Cardiopatia Reumática/complicações , Cardiopatia Reumática/diagnóstico , Transplante de Coração/métodos , Pessoa de Meia-Idade , Calcinose/cirurgia , Calcinose/diagnóstico , Calcinose/complicações , Átrios do Coração/diagnóstico por imagem , Átrios do Coração/cirurgia , Insuficiência Cardíaca/cirurgia , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/diagnóstico , Índice de Gravidade de Doença , Resultado do Tratamento , Implante de Prótese de Valva Cardíaca/métodos , Pericárdio/transplante , Pericárdio/cirurgia
17.
Clin Oral Investig ; 28(5): 300, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38704784

RESUMO

OBJECTIVE: The primary objective of this review is to compare autogenous soft tissue grafts (connective tissue graft - CTG and free gingival graft-FGG) with different type of matrices (acellular dermal matrix-ADM, xenograft collagen matrix-XCM, volume-stable collagen matrix-VCMX) used to increase peri-implant soft tissues. MATERIALS AND METHODS: A search on electronic databases was performed to identify randomized and non-randomized controlled trials (RCTs and CCTs, respectively) with either parallel or split-mouth design, and treating ≥ 10 patients. A network meta-analysis (NMA) was used to compare different matrices. Soft tissue thickness dimensional changes and keratinized width (KMW) changes were the primary outcome measures. The secondary outcomes were to evaluate: a) PROMs; b) volumetric changes; c) surgical operating time; and d) different periodontal measurements. RESULTS: A total of 23 studies were included in the qualitative analysis, and 16 studies (11 RCTs and 5 CCTs) in the quantitative analysis. A total of N = 573 sites were evaluated for NMA. CTG resulted the best material for increasing peri-implant soft tissue thickness, at 180 and 360 days after surgery. The use of an ADM showed good results for buccal thickness increase, primarily in the first three months after surgery. Vestibuloplasty + FGG resulted in the most effective technique for peri-implant KMW augmentation, after 180 days. CONCLUSIONS: While CTG demonstrated better performance in all the comparison and FGG showed to be the best graft to increase keratinized mucosa up to 90 days, ADM and VCMX may be used to increase soft tissue horizontal thickness with lower patients' morbidity. LIMITATIONS: The limits of this NMA are the following: a) limited number of included studies; b) high heterogeneity among them (number of patients, treatment sites, surgical techniques, outcome measures, and follow-ups). CLINICAL RELEVANCE: Many studies compared the efficacy of autogenous and non-autogenous grafts in terms of gingival thickness, volume, and keratinized width increase. However, there is still not clear overall evidence on this topic. This NMA helps clinicians to choose the right material in different peri-implant soft tissue procedures. Recommendations for future studies are mandatory.


Assuntos
Colágeno , Metanálise em Rede , Humanos , Colágeno/uso terapêutico , Gengiva/transplante , Derme Acelular , Tecido Conjuntivo/transplante , Implantes Dentários , Gengivoplastia/métodos
18.
Nat Commun ; 15(1): 3904, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38724502

RESUMO

Chronic wounds are a major complication in patients with diabetes. Here, we identify a therapeutic circRNA and load it into small extracellular vesicles (sEVs) to treat diabetic wounds in preclinical models. We show that circCDK13 can stimulate the proliferation and migration of human dermal fibroblasts and human epidermal keratinocytes by interacting with insulin-like growth factor 2 mRNA binding protein 3 in an N6-Methyladenosine-dependent manner to enhance CD44 and c-MYC expression. We engineered sEVs that overexpress circCDK13 and show that local subcutaneous injection into male db/db diabetic mouse wounds and wounds of streptozotocin-induced type I male diabetic rats could accelerate wound healing and skin appendage regeneration. Our study demonstrates that the delivery of circCDK13 in sEVs may present an option for diabetic wound treatment.


Assuntos
Proliferação de Células , Diabetes Mellitus Experimental , Vesículas Extracelulares , Fibroblastos , Queratinócitos , RNA Circular , Cicatrização , Animais , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/transplante , Cicatrização/efeitos dos fármacos , Humanos , Masculino , Camundongos , Ratos , Fibroblastos/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , Queratinócitos/metabolismo , Movimento Celular , Pele/metabolismo , Receptores de Hialuronatos/metabolismo , Receptores de Hialuronatos/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteínas Proto-Oncogênicas c-myc/genética , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , Ratos Sprague-Dawley , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética
19.
Cells ; 13(9)2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38727297

RESUMO

Spinal fusion, a common surgery performed for degenerative lumbar conditions, often uses recombinant human bone morphogenetic protein 2 (rhBMP-2) that is associated with adverse effects. Mesenchymal stromal/stem cells (MSCs) and their extracellular vesicles (EVs), particularly exosomes, have demonstrated efficacy in bone and cartilage repair. However, the efficacy of MSC exosomes in spinal fusion remains to be ascertained. This study investigates the fusion efficacy of MSC exosomes delivered via an absorbable collagen sponge packed in a poly Ɛ-caprolactone tricalcium phosphate (PCL-TCP) scaffold in a rat posterolateral spinal fusion model. Herein, it is shown that a single implantation of exosome-supplemented collagen sponge packed in PCL-TCP scaffold enhanced spinal fusion and improved mechanical stability by inducing bone formation and bridging between the transverse processes, as evidenced by significant improvements in fusion score and rate, bone structural parameters, histology, stiffness, and range of motion. This study demonstrates for the first time that MSC exosomes promote bone formation to enhance spinal fusion and mechanical stability in a rat model, supporting its translational potential for application in spinal fusion.


Assuntos
Exossomos , Células-Tronco Mesenquimais , Ratos Sprague-Dawley , Fusão Vertebral , Animais , Exossomos/metabolismo , Exossomos/transplante , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia , Fusão Vertebral/métodos , Ratos , Osteogênese/efeitos dos fármacos , Fosfatos de Cálcio/farmacologia , Masculino , Humanos , Alicerces Teciduais/química , Proteína Morfogenética Óssea 2/metabolismo , Transplante de Células-Tronco Mesenquimais/métodos
20.
Clin Oral Investig ; 28(5): 291, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38691209

RESUMO

OBJECTIVE: This split-mouth randomized study aimed to assess efficacy of leucocyte-platelet-rich fibrin (L-PRF) versus connective tissue graft (CTG) in achieving root coverage (RC) for multiple adjacent gingival recessions (MAGRs) throughout 12-month period. MATERIALS AND METHODS: The study enrolled 59 teeth from 12 patients with Miller Class I MAGRs ≥ 2 mm on bilateral or contralateral sides. Patients were randomly assigned to receive coronally advanced flap (CAF) with either CTG (control) or L-PRF (test) treatment. Various parameters, including plaque and gingival index, clinical attachment level, recession depth, probing depth, recession width (RW), papilla width (PW), keratinized tissue width (KTW), gingival thickness (GT), percentage of RC, complete root coverage (CRC), and location of the relative gingival margin concerning the cemento-enamel junctions (GMCEJ) after CAF, were recorded at baseline, 3-, 6-, and 12-months post-surgery. On June 29, 2021 the study was registred to ClinicalTrials.gov (NCT04942821). RESULTS: Except KTW and GT gain, all clinical parameters, RC, and CRC were similar between the groups at all follow-up periods (p > 0.05). The higher GT and KTW gains were detected in the control group compared to test group at 12 months (p < 0.05). Both RC and CRC were positively associated with initial PW and GMCEJ, but negatively with initial RW (p < 0.05). CONCLUSIONS: The current study concludes that L-PRF were equally effective as CTG in treating MAGRs in terms of RC and CRC. Additionally, RC and CRC outcomes appeared to be influenced by GMCEJ, PW, and RW. CLINICAL RELEVANCE: L-PRF could represent a feasible substitute for CTG in treating MAGRs.


Assuntos
Retração Gengival , Fibrina Rica em Plaquetas , Retalhos Cirúrgicos , Humanos , Retração Gengival/cirurgia , Masculino , Feminino , Adulto , Leucócitos , Pessoa de Meia-Idade , Índice Periodontal , Tecido Conjuntivo/transplante , Resultado do Tratamento
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