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1.
Mediators Inflamm ; 2021: 6694109, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33976586

RESUMO

Background: Allergic rhinitis (AR) affects millions of people and is lack of effective treatment. CD40 is an important costimulatory molecule in immunity. However, few studies have focused on the role of CD40 in AR. Methods: In this study, we built mouse model of chronic AR. The mice were divided into the AR, control, intravenous CD40 siRNA, and nasal CD40 siRNA groups (n = 6 each). We detected OVA-sIgE, IL-4, IL-5, IL-13, IL-10, IFN-γ, and TGF-ß levels in serum and supernatant by ELISA, CD40+ splenic DCs, and Foxp3+ Tregs by flow cytometry and CD40 mRNA by RT2-PCR. We also used PAS and MT stains to assess tissue remodelling. Results: (1) The OVA-sIgE, IL-4, IL-5, and IL-13 levels in the serum or supernatant of nasal septal membrane of AR mice were significantly higher than control. After treated with CD40 siRNA, those indicators were significantly decreased. The IFN-γ, IL-10, and TGF-ß levels in AR mice were significantly lower than that in control and were increased by administration of CD40 siRNA. (2) AR mice had significantly fewer Foxp3+ Tregs in the spleen than control mice. After treated with CD40 siRNA, AR mice had significantly more Foxp3+ Tregs. (3) AR mice exhibited a significantly higher CD40 mRNA levels than control. Administration of CD40 siRNA significantly reduced the CD40 mRNA level. (4) The AR mice showed significantly greater collagen deposition than the control in MT staining. Applications of CD40 siRNA significantly reduced the collagen deposition in AR mice. Conclusion: CD40 siRNA therapy shows promise for chronic AR as it significantly attenuated allergic symptoms and Th2-related inflammation and upregulated Foxp3+ Tregs. CD40 plays a role in tissue remodelling in AR, which can be inhibited by CD40 siRNA application.

3.
Cells ; 10(3)2021 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-33805763

RESUMO

Cardiovascular disease (CVD) is still the leading cause of death worldwide. Coronary artery occlusion, or myocardial infarction (MI) causes massive loss of cardiomyocytes. The ischemia area is eventually replaced by a fibrotic scar. From the mechanical dysfunctions of the scar in electronic transduction, contraction and compliance, pathological cardiac dilation and heart failure develops. Once end-stage heart failure occurs, the only option is to perform heart transplantation. The sequential changes are termed cardiac remodeling, and are due to the lack of endogenous regenerative actions in the adult human heart. Regenerative medicine and biomedical engineering strategies have been pursued to repair the damaged heart and to restore normal cardiac function. Such strategies include both cellular and acellular products, in combination with biomaterials. In addition, substantial progress has been made to elucidate the molecular and cellular mechanisms underlying heart repair and regeneration. In this review, we summarize and discuss current therapeutic approaches for cardiac repair and provide a perspective on novel strategies that holding potential opportunities for future research and clinical translation.

4.
J Am Heart Assoc ; 10(8): e020402, 2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33821664

RESUMO

In the past decades, numerous preclinical studies and several clinical trials have evidenced the feasibility of cell transplantation in treating heart diseases. Over the years, different delivery routes of cell therapy have emerged and broadened the width of the field. However, a common hurdle is shared by all current delivery routes: low cell retention. A myriad of studies confirm that cell retention plays a crucial role in the success of cell-mediated cardiac repair. It is important for any delivery route to maintain donor cells in the recipient heart for enough time to not only proliferate by themselves, but also to send paracrine signals to surrounding damaged heart cells and repair them. In this review, we first undertake an in-depth study of primary theories of cell loss, including low efficiency in cell injection, "washout" effects, and cell death, and then organize the literature from the past decade that focuses on cell transplantation to the heart using various cell delivery routes, including intracoronary injection, systemic intravenous injection, retrograde coronary venous injection, and intramyocardial injection. In addition to a recapitulation of these approaches, we also clearly evaluate their strengths and weaknesses. Furthermore, we conduct comparative research on the cell retention rate and functional outcomes of these delivery routes. Finally, we extend our discussion to state-of-the-art bioengineering techniques that enhance cell retention, as well as alternative delivery routes, such as intrapericardial delivery. A combination of these novel strategies and more accurate assessment methods will help to address the hurdle of low cell retention and boost the efficacy of cell transplantation to the heart.

5.
Oncologist ; 2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33830591

RESUMO

LESSONS LEARNED: Bevacizumab combined with S-1 and raltitrexed demonstrated positive antitumor efficacy and acceptable toxicity. This combination might represent a treatment option for refractory metastatic colorectal cancer. BACKGROUND: In patients with metastatic colorectal cancer (mCRC) refractory to standard therapies, S-1 plus raltitrexed showed a good objective response rate (ORR) and significant survival benefit in our previous study. In the present study, we assessed the activity and safety of bevacizumab combined with S-1 and raltitrexed. METHODS: This investigator-initiated, open-label, single-arm, phase II trial was performed at West China Hospital in China. Patients with mCRC who had disease progression after fluoropyrimidine, irinotecan, and oxaliplatin and had at least one measurable lesion were eligible for this trial. Anti-epidermal growth factor receptor (EGFR) (for tumors with wild-type RAS) and anti-vascular endothelial growth factor (VEGF) therapy in the first or second line was allowed, but patients who had been treated with bevacizumab across two consecutive chemotherapy regimens were excluded. Patients received bevacizumab (7.5 mg/kg on day 1), oral S-1 (80-120 mg per day for 14 days), and raltitrexed (3 mg/m2 on day 1) every 3 weeks. The primary endpoint was ORR. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and toxicity. RESULTS: From September 2015 to November 2019, 44 patients were enrolled. Tumor response evaluation was available in 44 patients at the time of the analysis. There were no complete responses; the ORR was 15.9%, and the disease control rate was 54.5%. Median PFS and OS were 110 days (95% confidence interval [CI], 65.0-155.0) and 367 days (95% CI, 310.4-423.6), respectively. The combination was well tolerated. CONCLUSION: Bevacizumab combined with S-1 and raltitrexed showed promising antitumor activity and safety in refractory mCRC.

6.
Sensors (Basel) ; 21(7)2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33918353

RESUMO

The increasing popularity of smartphones and location-based service (LBS) has brought us a new experience of mobile crowdsourcing marked by the characteristics of network-interconnection and information-sharing. However, these mobile crowdsourcing applications suffer from various inferential attacks based on mobile behavioral factors, such as location semantic, spatiotemporal correlation, etc. Unfortunately, most of the existing techniques protect the participant's location-privacy according to actual trajectories. Once the protection fails, data leakage will directly threaten the participant's location-related private information. It open the issue of participating in mobile crowdsourcing service without actual locations. In this paper, we propose a mobility-aware trajectory-prediction solution, TMarkov, for achieving privacy-preserving mobile crowdsourcing. Specifically, we introduce a time-partitioning concept into the Markov model to overcome its traditional limitations. A new transfer model is constructed to record the mobile user's time-varying behavioral patterns. Then, an unbiased estimation is conducted according to Gibbs Sampling method, because of the data incompleteness. Finally, we have the TMarkov model which characterizes the participant's dynamic mobile behaviors. With TMarkov in place, a mobility-aware spatiotemporal trajectory is predicted for the mobile user to participate in the crowdsourcing application. Extensive experiments with real-world dataset demonstrate that TMarkov well balances the trade-off between privacy preservation and data usability.

7.
Aging (Albany NY) ; 132021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33901015

RESUMO

This study aimed to investigate the role of long noncoding RNA (lncRNA) nuclear-enriched abundant transcript 1 (NEAT1) in the development of ALF. We collected blood samples from patients with acute liver failure (ALF) and established an ALF mouse model induced by D-galactosamine/Lipopolysaccharide (D-GalN/LPS) for in vivo studies. Peripheral blood mononuclear cells (PMBCs) induced with LPS were isolated for in vitro experiments. Survival tests, histological analysis, and biochemical indicator assays were conducted. Luciferase assay was performed to determine the binding affinity between microRNA-139 (miR-139) and p53-upregulated modulator of apoptosis (PUMA). Expression of lncRNA NEAT1, enhancer of zeste homolog 2 (EZH2), and PUMA was upregulated, while the expression of miR-139 was downregulated in clinical samples and D-GalN/LPS induced ALF mouse model. LncRNA NEAT1 promoted the enrichment of H3K27me3 on the promoter region of miR-139 via EZH2, which led to suppression of miR-139. The inhibition of miR-139 resulted in the upregulation of its downstream target PUMA. The NEAT1/miR-139/PUMA pathway upregulated the production of pro-inflammatory cytokines, tumor necrosis factor alpha, interleukin (IL)-6, and IL-1ß, thereby mediating the progression of ALF. In conclusion, silencing lncRNA NEAT1 upregulated the expression of miR-139 through EZH2, leading to the downregulation of PUMA, which alleviated the development of ALF.

8.
Nat Biomed Eng ; 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33820981

RESUMO

Drug-eluting stents implanted after ischaemic injury reduce the proliferation of endothelial cells and vascular smooth muscle cells and thus neointimal hyperplasia. However, the eluted drug also slows down the re-endothelialization process, delays arterial healing and can increase the risk of late restenosis. Here we show that stents releasing exosomes derived from mesenchymal stem cells in the presence of reactive oxygen species enhance vascular healing in rats with renal ischaemia-reperfusion injury, promoting endothelial cell tube formation and proliferation, and impairing the migration of smooth muscle cells. Compared with drug-eluting stents and bare-metal stents, the exosome-coated stents accelerated re-endothelialization and decreased in-stent restenosis 28 days after implantation. We also show that exosome-eluting stents implanted in the abdominal aorta of rats with unilateral hindlimb ischaemia regulated macrophage polarization, reduced local vascular and systemic inflammation, and promoted muscle tissue repair.

9.
Adv Drug Deliv Rev ; 173: 504-519, 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33831476

RESUMO

Cardiac fibrosis remains an unresolved problem in heart diseases. After initial injury, cardiac fibroblasts (CFs) are activated and subsequently differentiate into myofibroblasts (myoFbs) that are major mediator cells in the pathological remodeling. MyoFbs exhibit proliferative and secretive characteristics, and contribute to extracellular matrix (ECM) turnover, collagen deposition. The persistent functions of myoFbs lead to fibrotic scars and cardiac dysfunction. The anti-fibrotic treatment is hindered by the elusive mechanism of fibrosis and lack of specific targets on myoFbs. In this review, we will outline the progress of cardiac fibrosis and its contributions to the heart failure. We will also shed light on the role of myoFbs in the regulation of adverse remodeling. The communication between myoFbs and other cells that are involved in the heart injury and repair respectively will be reviewed in detail. Then, recently developed therapeutic strategies to treat fibrosis will be summarized such as i) chimeric antigen receptor T cell (CAR-T) therapy with an optimal target on myoFbs, ii) direct reprogramming from stem cells to quiescent CFs, iii) "off-target" small molecular drugs. The application of nano/micro technology will be discussed as well, which is involved in the construction of cell-based biomimic platforms and "pleiotropic" drug delivery systems.

10.
Adv Nanobiomed Res ; : 2000063, 2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33681865

RESUMO

New infectious diseases are making themselves known as the human population grows, expands into new regions, and becomes more dense, increasing contact with each other and animal populations. Ease of travel has also increased infectious disease transmission and has now culminated into a global pandemic. The emergence of the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in December 2019 has already infected over 83.7 million people and caused over 1.8 million deaths. While there have been vaccine candidates produced and supportive care implemented, the world is impatiently waiting for a commercially approved vaccine and treatment for the coronavirus disease of 2019 (COVID-19). The different vaccine types investigated for the prevention of COVID-19 all have great promise but face safety obstacles that must be first addressed. Some vaccine candidates of key interest are whole inactivated viruses, adeno-associated viruses, virus-like particles, and lipid nanoparticles. This review examines nanobiomedical techniques for combatting COVID-19 in terms of vaccines and therapeutics.

11.
Biochem Biophys Res Commun ; 553: 114-118, 2021 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-33765555

RESUMO

Major depressive disorder (MDD) is a debilitating mental illness that can cause significant emotional disturbances and severe socioeconomic burdens. Rodent and nonhuman primate-based depression models have been studied, such as brain-derived neurotrophic factor (BDNF) and monoamine acid disorder hypotheses, as well as peripheral microbiota disturbances causing MDD; however, the pathogenesis is still largely unknown. This study aims to explore the relationship between ferritin and MDD. First, alterations in ferritin, including ferritin light chain (FTL) and ferritin heavy chain (FTH), in MDD patient plasma compared with healthy control (HC) plasma were detected using ELISA. Then, serum ferritin expression in cLPS-depressed mice was measured by ELISA. The existence of FTH in the hippocampus was validated by immunofluorescence, and the change in FTH levels in the hippocampus of mice injected with cLPS was detected by western blotting. FTL levels in MDD patients were decreased compared with those in HCs. In cLPS-depressed mice, serum ferritin was not different from that in the control group, while the expression of FTH in the hippocampus was significantly reduced in depressed mice. Our findings demonstrate the alteration of ferritin expression in MDD and provide new insight into the pathogenesis of MDD.

12.
Ann Palliat Med ; 10(2): 2167-2174, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33725772

RESUMO

BACKGROUND: In March 2020, the World Health Organization (WHO) declared COVID-19 a public health emergency of international concern. A small proportion of patients infected with COVID-19 go on to develop pneumonia. We speculated that COVID-19 may be likely to result in psychological disorders such as anxiety and depression. In this study, we conducted an investigation of anxiety and depression in patients with COVID-19. METHODS: Sixty-five COVID-19 patients were randomly enrolled into this study. Anxiety and depression among participants were measured through the completion of anonymous Chinese-language Zung self-rating anxiety scale and self-rating depression scale questionnaires. Data were analyzed using independent samples t-tests, Mann-Whitney U-tests, and χ2 tests. RESULTS: The questionnaire results showed that 26.15% and 41.54% of participants suffered from anxiety and depression, respectively, although there was no significantly statistical difference between the proportions of COVID-19 patients with anxiety and depression. Statistically significant differences in employment status, partial pressure of oxygen, and corticosteroid application existed between moderate- and severe COVID-19 patients (P<0.05). In particular, the partial pressure of oxygen was significantly lower in severe COVID-19 patients than in their moderate counter parts (71.31±23.54 vs. 101.06±34.43, U=156, P=0.006). Total lymphocytes was lower in severe group than in moderate group [1.659±0.643 vs. 0.745 (0.645, 0.928), U=109, P=0.000]. Also, a higher proportion of female than male patients had anxiety (χ2=5.388, P=0.02). COVID-19 patients who received antiviral medications also displayed a higher rate of anxiety (χ2=4.481, P=0.034). Total lymphocytes between the non-anxiety and anxiety had statistical difference (U=321, P=0.019). Meanwhile, total lymphocytes between the non-depression and depression also had statistical difference (U=389.5, P=0.01). CONCLUSIONS: Among patients with COVID-19, females and those treated with antiviral medications were more likely to experience anxiety. In addition, our findings reflected the effect of anxiety and depression on immune system.


Assuntos
Ansiedade/epidemiologia , Depressão/epidemiologia , Antivirais/uso terapêutico , China , Estudos Transversais , Feminino , Humanos , Linfócitos/citologia , Masculino , Inquéritos e Questionários
13.
Oncologist ; 2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33749934

RESUMO

LESSONS LEARNED: MET overexpression is uncommon, and positive MET immunohistochemistry (1+/2+) was an independent positive prognostic factor for response rate and progression-free survival. Whether MET overexpression can be considered a potential predictive biomarker and be used as an inclusion criterion is worth investigating in a future study. BACKGROUND: Metatinib tromethamine tablet (metatinib) is a small molecule receptor kinase inhibitor targeting both c-MET and vascular endothelial growth factor receptor 2. This phase I trial aimed to determine the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD), pharmacokinetics, safety, and efficacy of metatinib in patients with advanced solid tumors. METHODS: Eligible patients received a single dose of metatinib in a 3 + 3 dose-escalation design with dose levels of 25-800 mg/day, after a single dose on day 1, then 2 days off, and then a multidose schedule of once-daily doses for 25 consecutive days (days 4-28). Primary endpoints were MTD and safety; secondary and exploratory endpoints included pharmacokinetics (PK), efficacy, and biomarkers. RESULTS: Eighteen patients (including nine patients with hepatocellular carcinoma [HCC]) received at least one dose of study drug (one patient quit the study without continuous multiple-dose administration after receiving a single dose of metatinib). Hand-foot skin reaction, diarrhea, and liver dysfunction were the DLTs, and 200 mg/day was the MTD. The most common treatment-related adverse events (TRAEs) were skin toxicity (50%), diarrhea (33.3%), and liver dysfunction (27.8%). Three patients (only one of six in the 200 mg/day cohort; the other two in the 300 mg/day cohort) experienced severe TRAEs: one patient with severe liver dysfunction and two patients with severe liver dysfunction and skin toxicity, respectively. Pharmacokinetics assessment indicated that metatinib was rapidly absorbed and metabolized to the formation of reactive metabolite, SCR-1510, after single-dose administration. The mean time taken to achieve maximum concentration and terminal elimination half-life of SCR-1510 was approximately 2.0-3.0 hours and ranged from 8 to 14 hours. Two patients had partial responses. The objective response rate and disease control rate (DCR) were 11.1% and 61.1%, respectively. The median progression-free survival (PFS) was 2.75 months. CONCLUSION: Metatinib administration of 200 mg/day was well tolerated, safe, and effective. The MTD was 200 mg/day, which should be recommended in further investigations.

14.
Cell Death Dis ; 12(4): 310, 2021 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-33762578

RESUMO

SARS-CoV-2 is responsible for the ongoing world-wide pandemic which has already taken more than two million lives. Effective treatments are urgently needed. The enzymatic activity of the HECT-E3 ligase family members has been implicated in the cell egression phase of deadly RNA viruses such as Ebola through direct interaction of its VP40 Protein. Here we report that HECT-E3 ligase family members such as NEDD4 and WWP1 interact with and ubiquitylate the SARS-CoV-2 Spike protein. Furthermore, we find that HECT family members are overexpressed in primary samples derived from COVID-19 infected patients and COVID-19 mouse models. Importantly, rare germline activating variants in the NEDD4 and WWP1 genes are associated with severe COVID-19 cases. Critically, I3C, a natural NEDD4 and WWP1 inhibitor from Brassicaceae, displays potent antiviral effects and inhibits viral egression. In conclusion, we identify the HECT family members of E3 ligases as likely novel biomarkers for COVID-19, as well as new potential targets of therapeutic strategy easily testable in clinical trials in view of the established well-tolerated nature of the Brassicaceae natural compounds.


Assuntos
/tratamento farmacológico , Ubiquitina-Proteína Ligases/antagonistas & inibidores , Ubiquitina-Proteína Ligases/metabolismo , Adulto , Idoso , Animais , Antivirais/farmacologia , /metabolismo , Chlorocebus aethiops , Complexos Endossomais de Distribuição Requeridos para Transporte/metabolismo , Feminino , Humanos , Indóis/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Ubiquitina-Proteína Ligases Nedd4/genética , Ubiquitina-Proteína Ligases Nedd4/metabolismo , /metabolismo , Glicoproteína da Espícula de Coronavírus/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitinação , Células Vero
15.
Methods Mol Biol ; 2265: 417-425, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33704731

RESUMO

Cancer mortality rates are primarily a result of cancer metastasis. Recent advances in microscopy technology allow for the imaging of circulating tumor cells (CTCs) as they extravasate (exit) blood vessels, a key step in the metastasis process. Here, we describe the use of intravital microscopy techniques to image and isolate both extravasating melanoma CTCs and the extravasation-participating endothelial cells. These techniques can be used as a means to study cancer metastasis and as a screening tool for anticancer therapeutics.


Assuntos
Células Endoteliais , Microscopia Intravital , Melanoma Experimental , Células Neoplásicas Circulantes , Peixe-Zebra , Animais , Animais Geneticamente Modificados , Linhagem Celular Tumoral , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Melanoma Experimental/metabolismo , Melanoma Experimental/patologia , Metástase Neoplásica , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patologia
16.
Sci Total Environ ; 771: 145437, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33736182

RESUMO

Bacterial degradation is one of the most efficient ways to remove microcystins (MCs), the most frequently detected toxin in cyanobacterial blooms. Using Novosphingobium sp. ERW19 as a representative strain, our laboratory previously demonstrated that quorum sensing (QS), the cell density-dependent gene regulation system, positively regulates biodegradation of MCs via transcriptional activation of mlr-pathway-associated genes. Increasing evidence indicates that QS is involved in a wide spectrum of regulatory circuits, but it remains unclear which physiological processes in MC degradation besides the expression of MC-degrading genes are also subject to QS-dependent regulation. This study used transcriptome analysis to identify QS-regulated genes during degradation of MCs. A large percentage (up to 32.6%) of the genome of the MC-degrading bacterial strain Novosphingobium sp. ERW19 was significantly differentially expressed in the corresponding QS mutants. Pathway enrichment analysis of QS-regulated genes revealed that QS mainly influenced metabolism-associated pathways, particularly those related to amino acid metabolism, carbohydrate metabolism, and biodegradation and metabolism of xenobiotics. In-depth functional interpretation of QS-regulated genes indicated a variety of pathways were potentially associated with bacterial degradation or physiological responses to MCs, including genes involved in cell motility, cytochrome P450-dependent metabolism of xenobiotics, glutathione S-transferase (GST), envelope stress response, and ribosomes. Furthermore, QS may be involved in regulating the initial and final steps of the catabolic pathway of phenylacetic acid, an intermediate product of MC degradation. Collectively, this global survey of QS-regulated genes in a MC-degrading bacterial strain facilitates a deeper understanding of QS-controlled processes that may be important for bacterial degradation of MCs or may contribute to the physiological responses of bacteria to MCs.


Assuntos
Percepção de Quorum , Sphingomonadaceae , Biodegradação Ambiental , Perfilação da Expressão Gênica , Microcistinas , Sphingomonadaceae/genética
17.
Nanotechnology ; 2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33752183

RESUMO

An integration strategy of chemical welding and subsequent protection was demonstrated to address silver nanowires (Ag NWs)-based issues. Preferentially, a halogenated salt of NaCl solution was used to stimulate the junction welding thus to reduce the junction resistance, by virtue of the autocatalytic redox of Ag atoms with halogen ions and dissolved oxygen molecules. Subsequently, chitosan, possessing the biocompatible, degradable, environmentally friendly non-toxic features, was embedded to protect Ag NWs. With these two steps, the composite electrode consisting Ag NWs and chitosan reaches a lowest sheet resistance of ~8 Ω, with a transmittance over 80% at 550 nm, along with high thermal and chemical stabilities, accompanying with excellent flexibility. Besides, it also prompts a synergistic improvement when pioneered in Cu(In, Ga)Se2 (CIGS) device as a transparent conductive electrode (TCE). It yields a power conversion efficiency of 6.6%, with 32% improvement relative to that bare Ag NWs, and 85% of the conventional one. Our findings present a new strategy for addressing instable/inefficient Ag NWs-based devices, driving their rapid development and its practical applications.

18.
Nat Commun ; 12(1): 1412, 2021 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-33658506

RESUMO

Cardiac patches are an effective way to deliver therapeutics to the heart. However, such procedures are normally invasive and difficult to perform. Here, we develop and test a method to utilize the pericardial cavity as a natural "mold" for in situ cardiac patch formation after intrapericardial injection of therapeutics in biocompatible hydrogels. In rodent models of myocardial infarction, we demonstrate that intrapericardial injection is an effective and safe method to deliver hydrogels containing induced pluripotent stem cells-derived cardiac progenitor cells or mesenchymal stem cells-derived exosomes. After injection, the hydrogels form a cardiac patch-like structure in the pericardial cavity, mitigating immune response and increasing the cardiac retention of the therapeutics. With robust cardiovascular repair and stimulation of epicardium-derived cells, the delivered therapeutics mitigate cardiac remodeling and improve cardiac functions post myocardial infarction. Furthermore, we demonstrate the feasibility of minimally-invasive intrapericardial injection in a clinically-relevant porcine model. Collectively, our study establishes intrapericardial injection as a safe and effective method to deliver therapeutic-bearing hydrogels to the heart for cardiac repair.


Assuntos
Fármacos Cardiovasculares/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Hidrogéis/administração & dosagem , Infarto do Miocárdio/terapia , Animais , Procedimentos Cirúrgicos Cardíacos , Diferenciação Celular/fisiologia , Exossomos/metabolismo , Matriz Extracelular/química , Hidrogéis/química , Células-Tronco Pluripotentes Induzidas/transplante , Masculino , Teste de Materiais , Células-Tronco Mesenquimais/citologia , Camundongos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/patologia , Miócitos Cardíacos/citologia , Miócitos Cardíacos/fisiologia , Pericárdio , Ratos , Suínos
20.
Int Orthop ; 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33666766

RESUMO

BACKGROUND: Reconstructing bone structures and stabilizing adjacent joints are clinical challenges in treating talar necrosis and collapse (TNC). 3D printing technology has been demonstrated to improve the accuracy of talar replacement. This study aimed to evaluate anatomical talar replacement and the clinical results. METHODS: Nine patients with TNC were enrolled between 2016 and 2020. The prosthetic shape and size were designed by CT post-processing and mirror symmetry technology. The clinical outcomes included radiographic parameters of the forefoot, hindfoot, and ankle alignment, ankle activity, recurrent pain, and peri-operative complications. RESULTS: After a mean follow-up of 23.17 ± 6.65 months, degenerative arthritis and prosthetic dislocation and other complications were not observed on plain radiographs. Each 3D-printed talar prosthesis was placed in the original anatomical position. The parameters which have significant changes pre-operative and post-operative are as follows: talar height, 27.59 ± 5.99 mm and 34.56 ± 3.54 mm (95% CI - 13.05 to - 0.87, t = 2.94, P = 0.032) and Meary's angle, 11.73 ± 4.79° and 4.45 ± 1.82° (95% CI 1.29~22.44, t = 2.89, P = 0.034). The AOFAS hindfoot score improved from 26.33 ± 6.62 to 79.67 ± 3.14 at the final follow-up (95% CI 43.36~63.30, t = 13.75, P = 0.000). The VAS score decreased from 6.33 ± 1.03 to 0.83 ± 0.75 (95% CI 4.40~6.60, t = 12.84, P = 0.000). The post-operative satisfaction scores regarding pain relief, activities of daily living, and return to recreational activities were good to excellent, and the change of activity range was statistically significant. CONCLUSIONS: The 3D printing patient-specific total talar prostheses allowed anatomical reconstruction in TNC. This novel treatment with 3D-printed prostheses could serve as a reliable patient-specific alternative in TNC.

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