RESUMO
PURPOSE: Assessing whether single-lead ECG can be effectively and relatively inexpensively used in large-scale OSA screening, and identifying factors influencing moderate-to-severe OSA among elderly hypertensive patients without atypical symptoms in primary care. METHODS: The study gathered data from 15 medical institutions in Ningxia between January and December 2022 using cloud platforms. The dataset included basic information and 72-h ECG monitoring for 2573 hypertensive patients over 65. OSA screening was conducted using the single-lead wearable ECG devices based on the ACAT algorithm. A multivariable logistic regression identified the main factors affecting OSA severity in these patients, and the AUC was used to assess the model's predictive accuracy. RESULTS: The study found an OSA detection rate of 87.10%, with 55.42% being moderate to severe cases. Key risk factors associated with developing moderate-to-severe OSA included cardiac irregularities like supraventricular extrasystole and atrioventricular block, male gender, lifestyle factors like alcohol consumption and smoking, and health indicators such as SDNN ≤ 100 ms, abnormal LF/HF ratio, BMI, and age. The model's accuracy for predicting OSA, indicated by a ROAUC of 0.625, was moderate. Factors like gender, tea consumption, stroke history, and ventricular tachycardia were also independently linked to OSA severity. CONCLUSION: This study combines single-lead wearable ECG devices with the ACAT algorithm for OSA screening in Ningxia, China. Initial screening identified 87.10% of participants as having OSA, with 55.42% being moderate to severe cases. This suggests a convenient, low-cost, and repeatable ECG-based method for OSA screening, potentially improving early detection and management of OSA by identifying potential risk factors.
RESUMO
[Figure: see text].
Assuntos
Heme Oxigenase-1/metabolismo , Inflamassomos/metabolismo , Isquemia/enzimologia , Lisossomos/enzimologia , Macrófagos/enzimologia , Proteínas de Membrana/metabolismo , Músculo Esquelético/irrigação sanguínea , Músculo Esquelético/enzimologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Animais , Células Cultivadas , Bases de Dados Genéticas , Modelos Animais de Doenças , Heme Oxigenase-1/genética , Membro Posterior , Humanos , Inflamassomos/genética , Mediadores da Inflamação/metabolismo , Isquemia/genética , Isquemia/fisiopatologia , Masculino , Proteínas de Membrana/genética , Camundongos Endogâmicos C57BL , Camundongos Knockout , Músculo Esquelético/fisiopatologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Neovascularização Fisiológica , Proteólise , Recuperação de Função Fisiológica , Fluxo Sanguíneo RegionalRESUMO
BACKGROUND: Methylnaltrexone is a peripherally acting mu-opioid receptor antagonist that has been shown to relieve severe opioid-induced constipation (OIC) in patients with advanced disease receiving palliative care. Its efficacy remains unknown in cancer patients who are not terminally ill. The primary aim of this study was to evaluate the efficacy of methylnaltrexone over 48 h in cancer patients who were not terminally ill. METHODS: In this single-dose phase II trial, cancer patients with a prognosis of ≥3 months and OIC with <3 laxations during the preceding week were eligible. The primary endpoint was a rescue-free laxation ≤4 h after a single dose of methylnaltrexone. Friedman's two-way analysis of variance was conducted for the number of laxations, pain and withdrawal scales, and laxation- and constipation-related symptoms. Univariate/bivariate Cox proportional hazard models for laxation times were employed. RESULTS: Twelve patients received methylnaltrexone. Eleven patients had an ECOG performance status of 1 or 2. Four (33.3 %) and 5 (41.7 %) patients had rescue-free laxation within 4 and 24 h, respectively, and 10 (83.3 %) had laxation within 48 h (p = 0.006). Difficulty passing a stool improved significantly over 48 h (p = 0.029). The bivariate Cox models revealed that a shorter time to laxation was associated with a higher baseline morphine equivalent daily dose (hazard ratio, 1.02 per 1 mg; p = 0.018) and a smaller number of laxations in the preceding week (hazard ratio, 0.13 per one laxation; p = 0.035). Patients tolerated methylnaltrexone well without opioid withdrawal. CONCLUSIONS: Methylnaltrexone may relieve severe OIC in cancer patients who are not terminally ill. A larger prospective study is justified in this population. (NCT01004393, https://clinicaltrials.gov/show/NCT01004393 ).
Assuntos
Analgésicos Opioides/efeitos adversos , Constipação Intestinal/tratamento farmacológico , Naltrexona/análogos & derivados , Antagonistas de Entorpecentes/uso terapêutico , Neoplasias/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Constipação Intestinal/induzido quimicamente , Feminino , Humanos , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Naltrexona/uso terapêutico , Estadiamento de Neoplasias , Neoplasias/tratamento farmacológico , Prognóstico , Compostos de Amônio Quaternário/uso terapêuticoRESUMO
INTRODUCTION: Chronic systematic inflammation has been suggested to be associated with the occurrence and development of cardiovascular events. Low-grade systematic inflammation persists in type 2 diabetes mellitus (T2DM) patients. In addition, the risk of cerebral hemorrhage in these patients is increased compared with non-diabetic patients. Neutrophil-to-lymphocyte ratio (NLR) is the ratio derived by dividing the neutrophil count with the lymphocyte count from a peripheral blood sample. This study aimed to explore the relation between NLR and cerebral hemorrhage, and to prove that NLR is an independent risk factor of cerebral hemorrhage in T2DM patients. METHODS: In total, 429 cases of T2DM patients were included. The patients were divided into two groups depending on the presence of cerebral hemorrhage: the cerebral hemorrhage group (n = 87) and the control group (n = 342). Based on clinical and laboratory data of diabetes diagnosis, this article investigates the relationship between NLR and the risk of cerebral hemorrhage. RESULTS: Increase in NLR was positively correlated with the incidence of cerebral hemorrhage in T2DM patients and might serve as an independent risk factor of cerebral hemorrhage in T2DM patients (OR: 4.451, 95% CI: 2.582-7.672). NLR >2.58 might be useful in predicting the threshold value of cerebral hemorrhage risk in newly diagnosed T2DM patients (area under the curve: .72, 95% CI: .659-.780, P < .001) CONCLUSION: As an indicator of the degree of systematic inflammation, NLR is an independent risk factor of cerebral hemorrhage in T2DM patients.
Assuntos
Hemorragia Cerebral/sangue , Diabetes Mellitus Tipo 2/sangue , Inflamação/sangue , Linfócitos , Neutrófilos , Idoso , Área Sob a Curva , Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/etiologia , Distribuição de Qui-Quadrado , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Feminino , Humanos , Inflamação/complicações , Inflamação/diagnóstico , Modelos Logísticos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Valor Preditivo dos Testes , Curva ROC , Estudos Retrospectivos , Fatores de RiscoRESUMO
An increasing number of measurement electrodes have been designed to satisfy the demand for high-resolution detection using galvanic logging technology in complex formations. The forward modeling response analysis of logging tools has important guiding significance in the design of galvanic logging tools. Based on a three-dimensional finite element numerical simulation method, we established a forward model of galvanic multi-electrodes in a complex formation. We also designed a symmetrical resistance network model of the formation with equivalent resistance between two electrodes. A symmetrical resistance network was derived using the balanced bridge method. The asymmetrical admittance matrix was extended to a symmetrical extended admittance matrix to realize a convenient calculation of the equivalent symmetrical resistance network in complex formations. Verification of the microcolumn-focused logging tool, with nine electrodes in a simulated standard well, and an evaluation of the degree of invasion in an actual oil well indicate that this calibration method can improve the measurement accuracy of galvanic logging instruments.
Assuntos
Calibragem , Simulação por Computador , EletrodosRESUMO
OBJECTIVE: The purpose of the study described was to establish prediction models to initially screen the beneficiary patients with unresectable hepatocellular carcinoma (HCC) in the treatment of anti-vascular endothelial growth factor (VEGF) agents plus anti-programmed cell death-1 (PD-1) antibody. METHODS: A total of 62 patients were enrolled in this study. All patients underwent ultrasound (US), color ddoppler flowing imaging (CDFI), contrast-enhanced ultrasound (CEUS) and laboratory examinations within 2 wk before the treatment. Tumor response was assessed according to mRECIST criteria. Univariate and multivariate analyses were used to select the independent predictors. US + CDFI, CEUS and FULL models were established. Three models were displayed by nomography. Receiver operating characteristic (ROC) and calibration curves were drawn to evaluate the predictive ability of models. Decision curve analysis (DCA) was used to assess the clinical utility of models. RESULTS: On univariate and multivariate analysis, the US boundary (p = 0.037), halo (p = 0.002) and CDFI (p = 0.024) were included in the US + CDFI model. CEUS boundary (p = 0.001) and washout time (p < 0.001) were included in the CEUS model. The number of lesions (p = 0.104), halo on US (p = 0.014), CDFI (p = 0.057) and washout time on CEUS (p = 0.015) were incorporated into the FULL model. The C indices of the US + CDFI, CEUS and FULL models were 0.918, 0.920 and 0.973. CEUS and FULL models yielded a good net benefit for almost all threshold probabilities. CONCLUSION: Nomograms based on US, CDFI, CEUS and clinical characteristics could help to non-invasively predict the response to treatment with anti-PD-1 antibodies plus anti-VEGF agents.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Ultrassonografia , Fator A de Crescimento do Endotélio Vascular , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/tratamento farmacológico , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/tratamento farmacológico , Masculino , Feminino , Pessoa de Meia-Idade , Ultrassonografia/métodos , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Resultado do Tratamento , Idoso , Valor Preditivo dos Testes , Inibidores de Checkpoint Imunológico/uso terapêutico , Adulto , Meios de ContrasteRESUMO
BACKGROUND: Primary aldosteronism (P.A.) is the most common form of secondary hypertension, accounting for 5% of hypertensive patients and 17-23% of patients with resistant hypertension. Compared to primary hypertension, P.A. is more prone to cause severe organ damage and even early death. Adrenal venous sampling (AVS) is a practical confirmatory test for subtyping aldosterone-producing adenoma and bilateral adrenal hyperplasia, helping physicians to make an accurate decision between surgery or medication. According to guidelines, supine in bed before AVS is recommended for a desirable result of AVS. However, investigations about the most optimal preoperative supine time before AVS are lacking. METHODS/DESIGN: This is a multi-center prospective randomized controlled study. One hundred twenty patients diagnosed as P.A. and willing for AVS examination will be included. Participants will be randomly allocated to a 15-min supine time group or 2-h supine time group. The primary outcome is the degree of biochemical remission (serum potassium and orthostatic ARR). The secondary outcomes are degrees of clinical remission (blood pressure, type and dose of antihypertensive drugs), the technical success rate, and the adverse event of AVS (selective index ≥ 2 is considered successful surgery without corticotropin stimulation). DISCUSSION: P.A. is an intractable public health problem, and many techniques including AVS have been developed to identify this disease correctly. This study will help to understand whether the length of preoperative supine time would affect the diagnostic efficacy of AVS and thus help to formulate a more reasonable AVS procedure. TRIAL REGISTRATION: ClinicalTrials.gov NCT05658705. Registered on 10 September 2022.
Assuntos
Hiperaldosteronismo , Hipertensão , Humanos , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/cirurgia , Estudos Prospectivos , Aldosterona , Glândulas Suprarrenais , Hipertensão/complicações , Estudos RetrospectivosRESUMO
PIK3CA mutations occur in â¼8% of cancers, including â¼40% of HR-positive breast cancers, where the PI3K-alpha (PI3Kα)-selective inhibitor alpelisib is FDA approved in combination with fulvestrant. Although prior studies have identified resistance mechanisms, such as PTEN loss, clinically acquired resistance to PI3Kα inhibitors remains poorly understood. Through serial liquid biopsies and rapid autopsies in 39 patients with advanced breast cancer developing acquired resistance to PI3Kα inhibitors, we observe that 50% of patients acquire genomic alterations within the PI3K pathway, including PTEN loss and activating AKT1 mutations. Notably, although secondary PIK3CA mutations were previously reported to increase sensitivity to PI3Kα inhibitors, we identified emergent secondary resistance mutations in PIK3CA that alter the inhibitor binding pocket. Some mutations had differential effects on PI3Kα-selective versus pan-PI3K inhibitors, but resistance induced by all mutations could be overcome by the novel allosteric pan-mutant-selective PI3Kα-inhibitor RLY-2608. Together, these findings provide insights to guide strategies to overcome resistance in PIK3CA-mutated cancers. SIGNIFICANCE: In one of the largest patient cohorts analyzed to date, this study defines the clinical landscape of acquired resistance to PI3Kα inhibitors. Genomic alterations within the PI3K pathway represent a major mode of resistance and identify a novel class of secondary PIK3CA resistance mutations that can be overcome by an allosteric PI3Kα inhibitor. See related commentary by Gong and Vanhaesebroeck, p. 204 . See related article by Varkaris et al., p. 240 . This article is featured in Selected Articles from This Issue, p. 201.
Assuntos
Neoplasias da Mama , Fosfatidilinositol 3-Quinases , Humanos , Feminino , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Fulvestranto , Inibidores de Fosfoinositídeo-3 Quinase , Classe I de Fosfatidilinositol 3-Quinases/genética , MutaçãoRESUMO
PIK3CA (PI3Kα) is a lipid kinase commonly mutated in cancer, including â¼40% of hormone receptor-positive breast cancer. The most frequently observed mutants occur in the kinase and helical domains. Orthosteric PI3Kα inhibitors suffer from poor selectivity leading to undesirable side effects, most prominently hyperglycemia due to inhibition of wild-type (WT) PI3Kα. Here, we used molecular dynamics simulations and cryo-electron microscopy to identify an allosteric network that provides an explanation for how mutations favor PI3Kα activation. A DNA-encoded library screen leveraging electron microscopy-optimized constructs, differential enrichment, and an orthosteric-blocking compound led to the identification of RLY-2608, a first-in-class allosteric mutant-selective inhibitor of PI3Kα. RLY-2608 inhibited tumor growth in PIK3CA-mutant xenograft models with minimal impact on insulin, a marker of dysregulated glucose homeostasis. RLY-2608 elicited objective tumor responses in two patients diagnosed with advanced hormone receptor-positive breast cancer with kinase or helical domain PIK3CA mutations, with no observed WT PI3Kα-related toxicities. SIGNIFICANCE: Treatments for PIK3CA-mutant cancers are limited by toxicities associated with the inhibition of WT PI3Kα. Molecular dynamics, cryo-electron microscopy, and DNA-encoded libraries were used to develop RLY-2608, a first-in-class inhibitor that demonstrates mutant selectivity in patients. This marks the advance of clinical mutant-selective inhibition that overcomes limitations of orthosteric PI3Kα inhibitors. See related commentary by Gong and Vanhaesebroeck, p. 204 . See related article by Varkaris et al., p. 227 . This article is featured in Selected Articles from This Issue, p. 201.
Assuntos
Neoplasias da Mama , Hiperinsulinismo , Humanos , Feminino , Inibidores de Fosfoinositídeo-3 Quinase/uso terapêutico , Microscopia Crioeletrônica , Neoplasias da Mama/tratamento farmacológico , Classe I de Fosfatidilinositol 3-Quinases/genética , Hiperinsulinismo/tratamento farmacológico , Hiperinsulinismo/genética , DNARESUMO
SCOPE: Phytosterols (PS) and sterol oxidation products are key dietary factors influencing atherosclerosis besides cholesterol, although the mechanisms remain elusive. Recently, single-cell RNA sequencing (scRNA-seq) has revealed the heterogeneity of multiple cell types associated with complex pathogenesis in atherosclerosis development. METHODS AND RESULTS: Here, scRNA-seq is performed to investigate the alterations in the aortic cells from ApoE-/- mice induced by diet-derived PS or two sterol oxidation products, phytosterols oxidation products (POPs), and cholesterol oxidation products (COPs). The study identifies four fibroblast subpopulations with different functions, and immunofluorescence demonstrates their spatial heterogeneity, providing evidence that suggests the transformation of smooth muscle cells (SMCs) and fibroblasts in atherosclerosis. The composition and gene expression profiles of aortic cells change broadly in response to PS/COPs/POPs exposure. Notably, PS exhibits an atheroprotective effect where different gene expressions are mainly found in B cells. Exposure to COPs accelerates atherosclerosis and results in marked alternations in myofibroblast subpopulations and T cells, while POPs only alter fibroblast subpopulations and B cells. CONCLUSION: The data elucidate the effects of dietary PS/COPs/POPs on aortic cells during atherosclerosis development, especially on the newly identified fibroblast subpopulations.
Assuntos
Aterosclerose , Fitosteróis , Animais , Camundongos , Fitosteróis/efeitos adversos , Fitosteróis/metabolismo , Esteróis/metabolismo , Transcriptoma , Colesterol/metabolismo , Aterosclerose/genética , Colesterol na DietaRESUMO
Perivascular adipose-derived stem cells (PV-ADSCs) could differentiate into smooth muscle cells (SMCs), participating in vascular remodeling. However, its underlying mechanism is not well explored. Our previous single-cell RNA-sequencing dataset identified a unique expression of matrix Gla protein (MGP) in PV-ADSCs compared with subcutaneous ADSCs. MGP involves in regulating SMC behaviors in vascular calcification and atherosclerosis. In this study, we investigated MGP's role in PV-ADSCs differentiation toward SMCs in vitro and in vascular remodeling in vivo. PV-ADSCs were isolated from perivascular regions of mouse aortas. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blot, and immunofluorescence confirmed higher MGP expression in PV-ADSCs. The MGP secretion increased along PV-ADSCs differentiation toward SMCs in response to transforming growth factor-beta 1 (TGF-ß1). Lentivirus knockdown of MGP markedly promoted the bone morphogenetic protein 2 (BMP2) expression and phosphorylation of SMAD1/5/8 in PV-ADSCs, subsequently inhibiting its differentiation toward SMCs. Such inhibition could be partially reversed by further application of BMP2 inhibitors. On the contrary, exogenous MGP inhibited BMP2 expression and SMAD1/5/8 phosphorylation in PV-ADSCs, thereby promoting its differentiation toward SMCs. Transplantation of cultured PV-ADSCs, which was pretreated by MGP knockdown, in mouse femoral artery guide-wire injury model significantly alleviated neointimal hyperplasia. In conclusion, MGP promoted the differentiation of PV-ADSCs toward SMCs through BMP2/SMAD-mediated signaling pathway. This study offers a supplement to the society of perivascular tissues and PV-ADSCs.
Assuntos
Proteína Morfogenética Óssea 2 , Proteínas da Matriz Extracelular , Animais , Proteína Morfogenética Óssea 2/metabolismo , Proteínas de Ligação ao Cálcio , Diferenciação Celular/fisiologia , Células Cultivadas , Proteínas da Matriz Extracelular/genética , Proteínas da Matriz Extracelular/metabolismo , Camundongos , Miócitos de Músculo Liso/metabolismo , Células-Tronco , Proteína de Matriz GlaRESUMO
Adipose-derived stem cells (ADSCs) can differentiate into vascular lineages and participate in vascular remodeling. Perivascular ADSCs (PV-ADSCs) draw attention because of their unique location. The heterogeneity of subcutaneous (SUB) and abdominal ADSCs were well addressed, but PV-ADSCs' heterogeneity has not been investigated. In this study, we applied single-cell analysis to compare SUB-ADSCs and PV-ADSCs regarding their subpopulations, functions, and cell fates. We uncovered four subpopulations of PV-ADSCs (Dpp4+, Col4a2+/Icam1+, Clec11a+/Cpe+, and Sult1e1+ cells), among which the Clec11a+ subpopulation potentially participated in and regulated PV-ADSC differentiation toward a smooth muscle cell (SMC) phenotype. Distinct characteristics between PV-ADSCs and SUB-ADSCs were revealed.
Assuntos
Vasos Sanguíneos/citologia , Células-Tronco/fisiologia , Gordura Subcutânea/citologia , Animais , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Camundongos , Camundongos Endogâmicos C57BL , Miócitos de Músculo Liso/fisiologia , Análise de Célula Única , Células-Tronco/citologiaRESUMO
Dendritic cells (DCs) are recognized as the most effective antigen-presenting cells at present. DCs have corresponding therapeutic effects in tumor immunity, transplantation immunity, infection inflammation and cardiovascular diseases, and the activation of T cells is dependent on DCs. However, normal bone-marrow-derived Dendritic cells (BMDCs) cultured on conventional culture plates are easy to be activated during culturing, and it is difficult to imitate the internal immune function. Here, we reported a novel BMDCs culturing with hydrogel substrate (CCHS), where we synthesized low substituted Gelatin Methacrylate-30 (GelMA-30) hydrogels and used them as a substitute for conventional culture plates in the culture and induction of BMDCs in vitro. The results showed that 5% GelMA-30 substrate was the best culture condition for BMDCs culturing. The low level of costimulatory molecules and the level of development-related transcription factors of BMDCs by CCHS were closer to that of spleen DCs and were capable of better promoting T cell activation and exerting an immune effect. CCHS was helpful to study the transformation of DCs from initial state to activated state, which contributes to the development of DC-T cell immunotherapy.
RESUMO
BACKGROUND: Perivascular adipose-derived stem cells (PVASCs) can contribute to vascular remodeling, which are also capable of differentiating into multiple cell lineages. The present study aims to investigate the mechanism of PVASC differentiation toward smooth muscle cells (SMCs) and endothelial cells (ECs) as well as its function in neointimal hyperplasia. METHODS: Single-cell sequencing and bulk mRNA sequencing were applied for searching key genes in PVASC regarding its role in vascular remodeling. PVASCs were induced to differentiate toward SMCs and ECs in vitro, which was quantitatively evaluated using immunofluorescence, quantitative real-time PCR (QPCR), and Western blot. Lentivirus transfections were performed in PVASCs to knock down or overexpress TBX20. In vivo, PVASCs transfected with lentivirus were transplanted around the guidewire injured femoral artery. Hematoxylin-eosin (H&E) staining was performed to examine their effects on neointimal hyperplasia. RESULTS: Bulk mRNA sequencing and single-cell sequencing revealed a unique expression of TBX20 in PVASCs. TBX20 expression markedly decreased during smooth muscle differentiation while it increased during endothelial differentiation of PVASCs. TBX20 knockdown resulted in the upregulation of SMC-specific marker expression and activated Smad2/3 signaling, while inhibiting endothelial differentiation. In contrast, TBX20 overexpression repressed the differentiation of PVASCs toward smooth muscle cells but promoted endothelial differentiation in vitro. Transplantation of PVASCs transfected with TBX20 overexpression lentivirus inhibited neointimal hyperplasia in a murine femoral artery guidewire injury model. On the contrary, neointimal hyperplasia significantly increased in the TBX20 knockdown group. CONCLUSION: A subpopulation of PVASCs uniquely expressed TBX20. TBX20 could regulate SMC and EC differentiation of PVASCs in vitro. Transplantation of PVASCs after vascular injury suggested that PVASCs participated in neointimal hyperplasia via TBX20.
RESUMO
[Figure: see text].
Assuntos
Calcineurina/metabolismo , Cálcio/metabolismo , Calpaína/metabolismo , Cardiomegalia/metabolismo , Canais Iônicos/metabolismo , Mecanotransdução Celular/fisiologia , Agonistas Adrenérgicos beta/farmacologia , Animais , Sinalização do Cálcio/efeitos dos fármacos , Sinalização do Cálcio/genética , Cardiomegalia/genética , Homeostase/efeitos dos fármacos , Homeostase/fisiologia , Canais Iônicos/genética , Isoproterenol/farmacologia , Camundongos , Camundongos Knockout , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Pirazinas/farmacologia , Ratos , Tiadiazóis/farmacologiaRESUMO
Bio-sourced hydrogels are attractive materials for diagnosing, repairing and improving the function of human tissues and organs. However, their mechanical strength decreases with an increase in water content. Furthermore, it is challenging to mold these hydrogels with high precision, which significantly limits their applications. Herein, we modified a biocompatible and biodegradable material, hyaluronic acid, with methacrylic anhydride and then cured it with a four-arm star structure cross-linking agent under ultraviolet light. The hyaluronic acid hydrogel was finally cured within 15 s with an adjustable cross-linking degree. The results demonstrated that the developed gel maintained good mechanical strength with a water content of 90%, while achieving micropatterns at a precision of 20 µm. The biological experiments showed that it could effectively promote the release of vascular endothelial growth factor (VEGF), which contributed to promoting cell growth, and has favorable biocompatibility. Overall, this hyaluronic acid hydrogel is a promising biomedical material with high forming accuracy, excellent mechanical properties, and favorable biocompatibility, which indicate its potential value in a variety of tissue engineering and biomedical applications.
Assuntos
Materiais Biocompatíveis/farmacologia , Ácido Hialurônico/farmacologia , Hidrogéis/farmacologia , Luz , Materiais Biocompatíveis/química , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Humanos , Ácido Hialurônico/química , Hidrogéis/química , Estrutura Molecular , Tamanho da Partícula , Propriedades de Superfície , Engenharia TecidualRESUMO
Cell therapy is a promising strategy in which living cells or cellular materials are delivered to treat a variety of diseases. Here, we developed an electrospray bioprinting method to rapidly generate cell-laden hydrogel microspheres, which limit the migration of the captured cells and provide an immunologically privileged microenvironment for cell survival in vivo. Currently, therapeutic angiogenesis aims to induce collateral vessel formation after limb ischemia. However, the clinical application of gene and cell therapy has been impeded by concerns regarding its inefficacy, as well as the associated risk of immunogenicity and oncogenicity. In this study, hydrogel microspheres encapsulating VEGF-overexpressing HEK293T cells showed good safety via subcutaneously injecting into male C57BL/6 mice. In addition, these cell-modified microspheres effectively promoted angiogenesis in a mouse hind-limb ischemia model. Therefore, we demonstrated the great therapeutic potential of this approach to induce angiogenesis in limb ischemia, indicating that bioprinting has a bright future in cell therapy.
Assuntos
Materiais Biocompatíveis/química , Microesferas , Neovascularização Fisiológica/fisiologia , Alginatos/química , Animais , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/uso terapêutico , Bioimpressão , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Células HEK293 , Membro Posterior/patologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Hidrogéis/química , Isquemia/terapia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neovascularização Fisiológica/efeitos dos fármacos , Alicerces Teciduais/química , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Obesity is an independent risk factor for cardiovascular disease. Adipose tissue was initially thought to be involved in metabolism through paracrine. Recent researches discovered mesenchymal stem cells inside adipose tissue which could differentiate into vascular lineages in vitro and in vivo, participating vascular remodeling. However, there were few researches focusing on distinct characteristics and functions of adipose-derived stem cells (ADSCs) from different regions. This is the first comprehensive review demonstrating the variances of ADSCs from the perspective of their origins.
Assuntos
Tecido Adiposo/citologia , Doenças Cardiovasculares/terapia , Transplante de Células-Tronco , Células-Tronco/fisiologia , HumanosRESUMO
INTRODUCTION: Adjuvant whole breast radiation therapy has developed into the standard of care for patients following a lumpectomy for early-stage breast cancer. However, there is recent interest in intraoperative radiation therapy (IORT) to minimize toxicity while still improving local control beyond surgical resection and anti-estrogen therapy alone. MATERIALS AND METHODS: All patients were evaluated pre-operatively in a multidisciplinary clinic setting at a community hospital for suitability for breast conservation therapy. A total of 109 patients were reviewed receiving 110 IORT treatments. Patients were followed with clinical breast examinations and mammography as clinically indicated. RESULTS: At a median follow-up of 29.9 months, 2/110 (1.8%) patients experienced a local failure. One patient (0.9%) experienced a regional failure. Local control, disease-free survival and overall survival at 3 years were 98.9% (95%CI 92.2-99.8), 97.2% (95%CI 88.9-99.3), and 96.0% (95%CI 84.9-99.0), respectively. Five-year local control, disease-free survival, and overall survival rates were 96.3% (95%CI 84.7-99.2), 94.6% (95%CI 83.2-98.3), and 92.5% (95%CI 80.4-97.3), respectively. Patient self-reported cosmetic outcome was available for 51 patients, with all patients reporting being either very pleased, pleased, or satisfied with their cosmetic outcome, and no patients reported being dissatisfied or worse. CONCLUSIONS: The results of our series suggest the feasibility of utilizing IORT in a community-based cancer center with a high degree of local control, and patient satisfaction with regard to cosmesis. While the results of this series suggest that IORT may be a promising modality, longer follow-up is warranted to better understand exactly which clinicopathological features can predict long-term locoregional disease control.
RESUMO
Statins have the potential to reduce breast cancer incidence and recurrence as shown in both epidemiologic and laboratory studies. The purpose of this study was to evaluate the effect of a lipophilic statin, atorvastatin, on breast cancer biomarkers of risk [mammographic density (MD) and insulin growth factor 1 (IGF-1)] in high-risk premenopausal women.Premenopausal women at increased risk for breast cancer received either 40 mg of atorvastatin or placebo for 1 year. Biomarker assessment was performed prior to initiation and at completion of study medication. MD was determined using both Breast Imaging Reporting and Data System and the visual analogue scale. Serum IGF-1 was determined by ELISA assay at the end of the study.Sixty-three women were enrolled between December 2005 and May 2010. Sixteen (25%) women withdrew. The mean age of participants was 43 (range, 35-50), 100% were white, and the average body mass index (BMI) was 26.4. The statin group demonstrated a significant decrease in cholesterol and low-density lipoprotein (LDL), suggesting compliance with study medication. After accounting for BMI, there was no difference in change in MD between groups. There was a significant increase in serum IGF-1 in the statin group.In this multi-institutional randomized prospective clinical trial of premenopausal women at increased risk for breast cancer, we did not see an effect of atorvastatin on MD. Further investigation of statins may be warranted; however, design of prior trials and potential mechanism of action of the agent need to be considered in the design of future trials. Cancer Prev Res; 9(5); 379-84. ©2016 AACR.