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1.
Univ. salud ; 27(1): B1-B9, enero-abril 2025. tab
Artigo em Espanhol | LILACS | ID: biblio-1554700

RESUMO

Introducción: Las enfermedades cerebrovasculares son consideradas un problema de salud pública que afectan muchas capacidades en el individuo, entre ellas la comunicación; de esta manera el cuidador cumple un papel fundamental en su recuperación. Objetivo: Describir el rol comunicativo del cuidador en la atención a pacientes con secuelas de accidente cerebrovascular en la ciudad de Sincelejo, Colombia. Materiales y métodos: Paradigma positivista, enfoque cuantitativo y estudio descriptivo de corte transversal realizado con 40 cuidadores, seleccionados según muestreo por criterios y reclutamiento en cadena. Se utilizó una encuesta sociodemográfica, una sobre favorecimiento y bienestar comunicativo y Escala Likert, se realizó análisis de fiabilidad y consistencia interna del instrumento. Resultados: Predominaron cuidadores de sexo femenino, sobresale el cuidador informal, con estudios de secundaria y estrato socioeconómico bajo. Se encontró una actitud favorable en la competencia del ser y saber hacer, prima el buen trato, justicia y respeto. La competencia del saber evidenció actitud desfavorable, caracterizada por un conocimiento limitado frente a la patología, insuficientes destrezas, técnicas y habilidades para cumplir sus funciones y estrategias empleadas. Conclusión: Es necesario cualificar al cuidador en la atención del paciente con accidente cerebrovascular, mediante programas de que dinamicen la competencia del ser, saber y saber hacer


Introduction: Cerebrovascular diseases are a public health problem affecting the different capabilities of patients, including communication. Thus, caregivers play a fundamental role in their recovery. Objective: To describe the communicative role of caregivers in the support of patients with stroke sequelae in the city of Sincelejo, Colombia. Materials and methods: A positivist paradigm, quantitative approach, and descriptive cross-sectional study was carried out with 40 caregivers, who were selected according to criteria sampling and chain recruitment. A sociodemographic survey about favorability and communicative well-being as well as the Likert Scale were applied. A reliability and internal consistency analysis was conducted. Results: The majority of caregivers were women. Informal caregivers, with high school education, and belonging to low socioeconomic status were also predominant. A positive attitude regarding competences such as being and knowing what to do; appropriate treatment of patients, with justice and respect, were observed as common features. The knowledge competence was considered unfavorable, which was characterized by limited understanding regarding pathology, strategies used, and insufficient skills, techniques, and abilities to fulfill their functions. Conclusions: Caregivers of stroke patients should be qualified through programs that improve the being, knowing, and knowing how to do competencies.


Introdução: As doenças cerebrovasculares são consideradas um problema de saúde pública que afeta diversas capacidades do indivíduo, incluindo a comunicação; desta forma, o cuidador desempenha um papel fundamental na sua recuperação. Objetivo: Descrever o papel comunicativo do cuidador no cuidado de pacientes com sequelas de acidente vascular cerebral na cidade de Sincelejo, Colômbia. Materiais e métodos: Paradigma positivista, abordagem quantitativa e estudo transversal descritivo realizado com 40 cuidadores, selecionados segundo critérios de amostragem e recrutamento em cadeia. Foi utilizado um inquérito sociodemográfico, um de favorabilidade e bem-estar comunicativo e uma Escala Likert, foi realizada uma análise da fiabilidade e consistência interna do instrumento. Resultados: Predominaram cuidadores do sexo feminino, destacando-se os cuidadores informais, com escolaridade média e baixo nível socioeconômico. Encontrou-se na competição uma atitude favorável por ser e saber fazer, prevalecendo o bom tratamento, a justiça e o respeito. A competência conhecimento apresentou atitude desfavorável, caracterizada por conhecimento limitado sobre a patologia, habilidades, técnicas e habilidades insuficientes para cumprir suas funções e estratégias utilizadas. Conclusões: É necessário qualificar o cuidador no cuidado ao paciente com AVC, por meio de programas que potencializem a competência de ser, saber e saber fazer.


Assuntos
Humanos , Masculino , Feminino
2.
FASEB J ; 38(13): e23785, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38949120

RESUMO

Cancer metastasis is the leading cause of death for those afflicted with cancer. In cancer metastasis, the cancer cells break off from the primary tumor, penetrate nearby blood vessels, and attach and extravasate out of the vessels to form secondary tumors at distant organs. This makes extravasation a critical step of the metastatic cascade. Herein, with a focus on triple-negative breast cancer, the role that the prospective secondary tumor microenvironment's mechanical properties play in circulating tumor cells' extravasation is reviewed. Specifically, the effects of the physically regulated vascular endothelial glycocalyx barrier element, vascular flow factors, and subendothelial extracellular matrix mechanical properties on cancer cell extravasation are examined. The ultimate goal of this review is to clarify the physical mechanisms that drive triple-negative breast cancer extravasation, as these mechanisms may be potential new targets for anti-metastasis therapy.


Assuntos
Glicocálix , Neoplasias de Mama Triplo Negativas , Microambiente Tumoral , Glicocálix/metabolismo , Glicocálix/patologia , Humanos , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/metabolismo , Feminino , Microambiente Tumoral/fisiologia , Animais , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patologia , Metástase Neoplásica , Endotélio Vascular/metabolismo , Endotélio Vascular/patologia
3.
Ann Biomed Eng ; 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38949730

RESUMO

PURPOSE: Through their contractile and synthetic capacity, vascular smooth muscle cells (VSMCs) can regulate the stiffness and resistance of the circulation. To model the contraction of blood vessels, an active stress component can be added to the (passive) Cauchy stress tensor. Different constitutive formulations have been proposed to describe this active stress component. Notably, however, measuring biomechanical behaviour of contracted blood vessels ex vivo presents several experimental challenges, which complicate the acquisition of comprehensive datasets to inform complex active stress models. In this work, we examine formulations for use with limited experimental contraction data as well as those developed to capture more comprehensive datasets. METHODS: First, we prove analytically that a subset of constitutive active stress formulations exhibits unstable behaviours (i.e., a non-unique diameter solution for a given pressure) in certain parameter ranges, particularly for large contractile deformations. Second, using experimental literature data, we present two case studies where these formulations are used to capture the contractile response of VSMCs in the presence of (1) limited and (2) extensive contraction data. RESULTS: We show how limited contraction data complicates selecting an appropriate active stress model for vascular applications, potentially resulting in unrealistic modelled behaviours. CONCLUSION: Our data provide a useful reference for selecting an active stress model which balances the trade-off between accuracy and available biomechanical information. Whilst complex physiologically motivated models' superior accuracy is recommended whenever active biomechanics can be extensively characterised experimentally, a constant 2nd Piola-Kirchhoff active stress model balances well accuracy and applicability with sparse contractile data.

4.
Arch Gynecol Obstet ; 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38963584

RESUMO

PURPOSE: Functional hypothalamic amenorrhea (FHA) is characterized by an estrogen deficiency which in turn can cause vascular dysfunction. The aim of this study is to evaluate any changes in the chorio-retinal circulation in patients affected by FHA. 24 patients with FHA and 24 age-matched controls underwent a gynecological evaluation and an OCT angiography (OCTA) to study chorio-retinal vascularization. RESULTS: OCTA in FHA patients showed an increase in vessel density in the choriocapillaris (CC) layer (both in the fovea area, at 5% p value = 0.037 and in the whole area, at 5% p value = 0.028) and an increase in vascular density in the deep fovea (DVP) (at 10% p value = 0.096) in the whole district compared to controls. Simple linear regressions show a significant negative association between CC vessel density and insulin (p = 0.0002) and glucose values (p = 0.0335) for the fovea district and a negative association between DVP vessel density and endometrial thickness (at 10%, p value: 0.095) in the whole district. CONCLUSION: Our study shows that CC vessel density is increased in women affected by FHA. This could represent a compensation effort to supply the vascular dysfunction caused by estrogen deficiency. We also found an increasing trend in vascular density in DVP associated with the decrease of endometrial thickness, an indirect sign of estrogenization. Considering that these changes occur in absence of visual defects, they could be used as a biomarker to estimate hypoestrogenism-induced microcirculation changes before clinical appearance.

5.
Int Ophthalmol ; 44(1): 312, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38963653

RESUMO

PURPOSE: To understand factors affecting visual prognosis and the number of intravitreal antivascular endothelial growth factor (anti-VEGF) injections needed to stabilize wet age-related macular degeneration (AMD). METHODS: In this retrospective cohort, 119 treatment-naïve wet AMD patients were followed for two years. In patients with bilateral disease, the eye with worse best-corrected visual acuity (BCVA) or that received more intravitreal injections was recruited as the study eye. In all visits, BCVA was recorded, ophthalmological examination was performed including macular optical coherence tomography imaging. Twenty health status/lifestyle questions were asked to the patients via phone as potential risk factors. All patients received 3 loading doses of intravitreal bevacizumab injections and received repeat injections of aflibercept or ranibizumab when the eye had a new, active neovascular lesion. RESULTS: Patients who took regular micronutrition had similar visual outcome and injection numbers compared to the ones who did not. Patients with bilateral disease needed less intravitreal injections compared to unilateral AMD patients (p = 0.016) and women on hormone replacement therapy (HRT) required less injections compared to the women who were not (p = 0.024). Female patients had a mean gain of 2.7 letters while male patients lost 3.8 letters (p = 0.038). Wet AMD started at an earlier age in smokers (p = 0.002). Patients with a better education level presented earlier with better BCVA (p = 0.037). CONCLUSION: HRT and anti-VEGF injections to the fellow eye improved the prognosis of wet AMD, while male patients had slightly worse prognosis. Estrogen's protective effects and potential contribution in wet AMD needs further attention. Retrospectively registered: 2020/0622.


Assuntos
Inibidores da Angiogênese , Bevacizumab , Injeções Intravítreas , Ranibizumab , Receptores de Fatores de Crescimento do Endotélio Vascular , Proteínas Recombinantes de Fusão , Tomografia de Coerência Óptica , Fator A de Crescimento do Endotélio Vascular , Acuidade Visual , Degeneração Macular Exsudativa , Humanos , Masculino , Estudos Retrospectivos , Feminino , Degeneração Macular Exsudativa/tratamento farmacológico , Degeneração Macular Exsudativa/diagnóstico , Degeneração Macular Exsudativa/fisiopatologia , Inibidores da Angiogênese/administração & dosagem , Idoso , Ranibizumab/administração & dosagem , Receptores de Fatores de Crescimento do Endotélio Vascular/administração & dosagem , Receptores de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Proteínas Recombinantes de Fusão/administração & dosagem , Bevacizumab/administração & dosagem , Tomografia de Coerência Óptica/métodos , Prognóstico , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Idoso de 80 Anos ou mais , Seguimentos , Pessoa de Meia-Idade , Angiofluoresceinografia/métodos
6.
Sci Rep ; 14(1): 15086, 2024 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956152

RESUMO

Elevated levels of the gut pro-hormone Proneurotensin (proNT) have been found to predict development of cardiovascular disease. However, it is still unknown whether higher proNT levels are associated with subclinical vascular damage. Herein, we investigated the relationship between higher proNT concentrations and augmented pulse pressure (PP) and carotid intima-media thickness (cIMT), indicators of increased arterial stiffness and subclinical atherosclerosis, respectively. Clinical characteristics, PP and cIMT were evaluated in 154 non-diabetic individuals stratified into tertiles according to fasting serum proNT concentrations. We found that, subjects with higher proNT levels exhibited a worse lipid profile and insulin sensitivity, increased C-reactive protein levels, along with higher values of PP and cIMT as compared to the lowest proNT tertile. Prevalence of elevated PP (≥ 60 mmHg) and subclinical carotid atherosclerosis (IMT > 0.9 mm) was increased in the highest tertile of proNT. In a logistic regression analysis adjusted for several confounders, subjects with higher proNT levels displayed a fivefold raised risk of having elevated PP values (OR 5.36; 95%CI 1.04-27.28; P = 0.05) and early carotid atherosclerosis (OR 4.81; 95%CI 1.39-16.57; P = 0.01) as compared to the lowest proNT tertile. In conclusion, higher circulating levels of proNT are a biomarker of subclinical vascular damage independent of other atherosclerotic risk factors.


Assuntos
Pressão Sanguínea , Espessura Intima-Media Carotídea , Precursores de Proteínas , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Precursores de Proteínas/sangue , Adulto , Neurotensina/sangue , Doenças das Artérias Carótidas/sangue , Rigidez Vascular , Fatores de Risco , Proteína C-Reativa/metabolismo , Proteína C-Reativa/análise , Biomarcadores/sangue , Aterosclerose/sangue , Idoso
7.
Front Cell Dev Biol ; 12: 1389607, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38961866

RESUMO

Mural cells are critically important for the development, maturation, and maintenance of the blood vasculature. Pericytes are predominantly observed in capillaries and venules, while vascular smooth muscle cells (VSMCs) are found in arterioles, arteries, and veins. In this study, we have investigated functional differences between human pericytes and human coronary artery smooth muscle cells (CASMCs) as a model VSMC type. We compared the ability of these two mural cells to invade three-dimensional (3D) collagen matrices, recruit to developing human endothelial cell (EC)-lined tubes in 3D matrices and induce vascular basement membrane matrix assembly around these tubes. Here, we show that pericytes selectively invade, recruit, and induce basement membrane deposition on EC tubes under defined conditions, while CASMCs fail to respond equivalently. Pericytes dramatically invade 3D collagen matrices in response to the EC-derived factors, platelet-derived growth factor (PDGF)-BB, PDGF-DD, and endothelin-1, while minimal invasion occurs with CASMCs. Furthermore, pericytes recruit to EC tube networks, and induce basement membrane deposition around assembling EC tubes (narrow and elongated tubes) when these cells are co-cultured. In contrast, CASMCs are markedly less able to perform these functions showing minimal recruitment, little to no basement membrane deposition, with wider and shorter tubes. Our new findings suggest that pericytes demonstrate much greater functional ability to invade 3D matrix environments, recruit to EC-lined tubes and induce vascular basement membrane matrix deposition in response to and in conjunction with ECs.

9.
bioRxiv ; 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38948880

RESUMO

Capillary malformations (CM) are congenital vascular irregularities of capillary and venous blood vessels that appear in the skin, leptomeninges of the brain, and the choroid of the eye in the disorder known as Sturge Weber Syndrome (SWS). More common are non-syndromic CM found only in the skin, without brain or ocular involvement. A somatic activating mutation in GNAQ (p.R183Q) is found in ~90% of syndromic and non-syndromic CM specimens and is present in CD31pos endothelial cells isolated from brain and skin CM specimens. Endothelial expression of the GNAQ p.R183Q variant is sufficient to form CM-like vessels in mice. Given the distinct features and functions of blood vessels in the brain versus the skin, we examined the features of CM vessels in both tissues to gain insights into the pathogenesis of CM. Herein, we present morphologic characteristics of CM observed in specimen from brain and skin. The GNAQ p.R183Q variant allelic frequency in each specimen was determined by droplet digital PCR. Sections were stained for endothelial cells, tight junctions, mural cells, and macrophages to assess the endothelium as well as perivascular constituents. CM blood vessels in brain and skin were enlarged, exhibited fibrin leakage and reduced zona occludin-1, and were surrounded by MRC1pos/LYVE1pos macrophages. In contrast, the CMs from brain and skin differ in endothelial sprouting activity and localization of mural cells. These characteristics might be helpful in the development of targeted and/or tissue specific therapies to prevent or reverse non-syndromic and syndromic CM.

10.
BMJ Open ; 14(6): e079038, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38951003

RESUMO

BACKGROUND: Non-small cell lung cancer (NSCLC) has a poor prognosis. Transvascular intervention is an important approach for treating NSCLC. Drug-eluting bead bronchial artery chemoembolisation (DEB-BACE) is a technique of using DEBs loaded with chemotherapeutic drugs for BACE. This study aims to conduct a meta-analysis to comprehensively assess the effectiveness and safety of DEB-BACE in treating NSCLC and investigate a novel therapeutic strategy for NSCLC. METHODS AND ANALYSIS: Wanfang, China National Knowledge Infrastructure, Medline (via PubMed), Cochrane Library, Scopus and Embase databases will be searched in November 2024. A meta-analysis will be conducted to assess the effectiveness and safety of DEB-BACE in the treatment of NSCLC. The following keywords will be applied: "Carcinoma, Non-Small-Cell Lung", "Non-Small Cell Lung Cancer", "Drug-Eluting Bead Bronchial Arterial Chemoembolization" and "drug-eluting beads". Reports in Chinese or English comparing the efficacy of DEB-BACE with other NSCLC treatment options will be included. Case reports, single-arm studies, conference papers, abstracts without full text and reports published in languages other than English and Chinese will not be considered. The Cochrane Handbook for Systematic Reviews of Interventions will be used to independently assess the risk of bias for each included study. In case of significant heterogeneity between studies, possible sources of heterogeneity will be explored through subgroup and sensitivity analysis. For the statistical analysis of the data, RevMan V.5.3 will be used. ETHICS AND DISSEMINATION: This meta-analysis will seek publication in a peer-reviewed journal on completion. Ethical approval is not required for this study as it is a database-based study. PROSPERO REGISTRATION NUMBER: CRD42023411392.


Assuntos
Artérias Brônquicas , Carcinoma Pulmonar de Células não Pequenas , Quimioembolização Terapêutica , Neoplasias Pulmonares , Metanálise como Assunto , Humanos , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Quimioembolização Terapêutica/métodos , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/tratamento farmacológico , Projetos de Pesquisa
11.
Mol Neurobiol ; 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38990251

RESUMO

Synaptic dysfunction is considered the best neuropathological correlate of cognitive decline in vascular dementia (VaD). However, the alterations of synaptic proteins at the synaptosomal level in VaD remain unclear. In this study, a VaD model was established in male rats using bilateral common carotid artery occlusion (2VO). We performed a novel object recognition task to evaluate cognitive impairment. Immunohistochemistry was used to assess the expression of neuron-specific nuclear binding protein (NeuN). Brain synaptosomes were isolated and subjected to label-free proteomic analysis to quantify and identify the synaptic features of differentially expressed proteins (DEPs). Synaptic and hub protein expression was detected in synaptosomes using western blotting. We found that male rats with VaD presented impaired memory and decreased NeuN protein expression in the cortex. Synaptosome proteomic analysis revealed 604 DEPs, with 493 and 111 markedly downregulated and upregulated proteins, respectively. KEGG analysis and SynGO annotation revealed that the synaptic vesicle (SV) cycle may be a key signaling pathway in VaD. Hub protein analysis of the main nodes in the protein network identified UBQLN2 and SV-related proteins, including CLTC, SNAP91, AP2S1, CLTA, VAMP2, EPN1, UBQLN2, AP2B1, AP2A2, and AP2M1. Western blotting showed that the levels of SV2A, CLTC, AP2S1, and VAMP2 decreased in the synaptosomes of 2VO rats, while UBQLN2 expression significantly increased. Our results suggest that the disruption in the presynaptic SV cycle is a key event in male rats with VaD, which could be characterized by the aberrant SV2A expression. SV-related proteins and UBQLN2 may be essential in synaptopathy. Thus, targeting the specific molecular markers in synaptosomes may be critical for the development of mechanism-directed therapies against VaD.

12.
Artigo em Alemão | MEDLINE | ID: mdl-38990311

RESUMO

The challenge in treating traumatic hemipelvectomy is the dynamics of the complex and life-threatening consequences of the injury. These include skin and soft tissue defects, osseous, neural and vascular injuries as well as the subsequent hemostatic derangement and organ dysfunction as part of the shock process. The treatment requires rapid and targeted decisions to save the patient's life. In this particular case a 34-year-old farmer was trapped between a wheeled loader and a stationary trailer. Upon arrival at the hospital the patient was in a state of hemorrhagic shock with accompanying acute traumatic coagulopathy and a grade III open pelvic trauma with complete ischemia of the left leg and a bladder injury. After performing emergency surgery and a two-stage approach for pelvic stabilization the patient's condition deteriorated up to multiorgan failure, necessitating left-sided hemipelvectomy as an immediate life-saving salvage procedure. In the further course multiple revision surgeries and plastic reconstructions due to wound infections and the presence of skin and soft tissue damage were required. Due to the rare confrontation with this type of injury in everyday practice and the absence of a universal treatment algorithm, the following case report is intended to contribute to a better understanding of the treatment and to illustrate the coherent interactions of the individual organ systems affected.

13.
Int Ophthalmol ; 44(1): 326, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38990443

RESUMO

PURPOSE: The aim of this study was to investigate the peripapillary choroidal vascular changes in thyroid orbitopathy (TO). METHODS: The study included 20 eyes of 10 patients with active TO (aTO), 30 eyes of 15 patients with inactive TO (inaTO) and 30 eyes of 30 healthy subjects. The peripapillary choroidal vascular change was assessed with peripapillary choroidal vascular index (pCVI), peripapillary choroidal luminal area (pLA), peripapillary choroidal stromal area (pSA), peripapillary total choroidal area (pTCA). RESULTS: Compared to the control group, there was a reduction in the nasal and temporal areas of pCVI in both the aTO and inaTO groups (aTO vs control: nasal p = 0.001 and temporal p = 0.004; inaTO vs control: nasal p = 0.007 and temporal p < 0.001), while the inferior area was lower only in the inaTO group (p = 0.001). Compared to the other groups, the inaTO group exhibited a decrease pSA (vs aTO: total p = 0.004, inferior p = 0.02 and vs control: total p = 0.01, inferior p = 0.03), pLA (vs aTO: total p = 0.02, inferior p = 0.02, temporal p < 0.001 and vs control: total p = 0.002, inferior p < 0.001, temporal p < 0.001) and pTCA (vs aTO: total p = 0.009, inferior p = 0.01, temporal p < 0.001 and vs control: total p = 0.003, inferior p = 0.001, temporal p < 0.001). CONCLUSION: The horizontal area (nasal and temporal area) of the peripapillary choroidal vascular structure may be more sensitive than the vertical area in TO patients. The first affected quadrant of RPC-VD in the active TO may be the inferior quadrant. Structural or vascular choroidal changes may occur during the chronic or post-active phase of the disease.


Assuntos
Corioide , Oftalmopatia de Graves , Disco Óptico , Tomografia de Coerência Óptica , Humanos , Corioide/irrigação sanguínea , Corioide/patologia , Corioide/diagnóstico por imagem , Masculino , Feminino , Oftalmopatia de Graves/diagnóstico , Oftalmopatia de Graves/patologia , Pessoa de Meia-Idade , Tomografia de Coerência Óptica/métodos , Adulto , Disco Óptico/irrigação sanguínea , Disco Óptico/patologia , Vasos Retinianos/patologia , Vasos Retinianos/diagnóstico por imagem , Acuidade Visual , Angiofluoresceinografia/métodos
14.
Res Sq ; 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38947000

RESUMO

Hereditary Hemorrhagic Telangiectasia (HHT) is a rare congenital disease in which fragile vascular malformations (VM) - including small telangiectasias and large arteriovenous malformations (AVMs) - focally develop in multiple organs. There are few treatment options and no cure for HHT. Most HHT patients are heterozygous for loss-of-function mutations affecting Endoglin (ENG) or Alk1 (ACVRL1); however, why loss of these genes manifests as VMs remains poorly understood. To complement ongoing work in animal models, we have developed a fully human, cell-based microphysiological model based on our Vascularized Micro-organ (VMO) platform (the HHT-VMO) that recapitulates HHT patient VMs. Using inducible ACVRL1 -knockdown, we control timing and extent of endogenous Alk1 expression in primary human endothelial cells (EC). Resulting HHT-VMO VMs develop over several days. Interestingly, in chimera experiments AVM-like lesions can be comprised of both Alk1-intact and Alk1-deficient EC, suggesting possible cell non-autonomous effects. Single cell RNA sequencing data are consistent with microvessel pruning/regression as contributing to AVM formation, while loss of PDGFB implicates mural cell recruitment. Finally, lesion formation is blocked by the VEGFR inhibitor pazopanib, mirroring positive effects of this drug in patients. In summary, we have developed a novel HHT-on-a-chip model that faithfully reproduces HHT patient lesions and that can be used to better understand HHT disease biology and identify potential new HHT drugs.

15.
Clin Sci (Lond) ; 138(14): 883-900, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-38959295

RESUMO

Hypertension is a leading risk factor for disease burden worldwide. Vascular contraction and remodeling contribute to the development of hypertension. Glutathione S-transferase P1 (Gstp1) plays several critical roles in both normal and neoplastic cells. In this study, we investigated the effect of Gstp1 on hypertension as well as on vascular smooth muscle cell (VSMC) contraction and phenotypic switching. We identified the higher level of Gstp1 in arteries and VSMCs from hypertensive rats compared with normotensive rats for the first time. We then developed Adeno-associated virus 9 (AAV9) mediated Gstp1 down-regulation and overexpression in rats and measured rat blood pressure by using the tail-cuff and the carotid catheter method. We found that the blood pressure of spontaneously hypertensive rats (SHR) rose significantly with Gstp1 down-regulation and reduced apparently after Gstp1 overexpression. Similar results were obtained from the observations of 2-kidney-1-clip renovascular (2K1C) hypertensive rats. Gstp1 did not influence blood pressure of normotensive Wistar-Kyoto (WKY) rats and Sprague-Dawley (SD) rats. Further in vitro study indicated that Gstp1 knockdown in SHR-VSMCs promoted cell proliferation, migration, dedifferentiation and contraction, while Gstp1 overexpression showed opposite effects. Results from bioinformatic analysis showed that the Apelin/APLNR system was involved in the effect of Gstp1 on SHR-VSMCs. The rise in blood pressure of SHR induced by Gstp1 knockdown could be reversed by APLNR antagonist F13A. We further found that Gstp1 enhanced the association between APLNR and Nedd4 E3 ubiquitin ligases to induce APLNR ubiquitination degradation. Thus, in the present study, we discovered a novel anti-hypertensive role of Gstp1 in hypertensive rats and provided the experimental basis for designing an effective anti-hypertensive therapeutic strategy.


Assuntos
Pressão Sanguínea , Glutationa S-Transferase pi , Hipertensão , Músculo Liso Vascular , Ubiquitina-Proteína Ligases Nedd4 , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Ratos Sprague-Dawley , Ubiquitinação , Animais , Ubiquitina-Proteína Ligases Nedd4/metabolismo , Ubiquitina-Proteína Ligases Nedd4/genética , Glutationa S-Transferase pi/metabolismo , Glutationa S-Transferase pi/genética , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Masculino , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Ratos , Proliferação de Células
16.
Free Radic Biol Med ; 222: 519-530, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38972612

RESUMO

BACKGROUND: Vascular oxidative stress and low-grade inflammation are important in the pathology of cardiovascular disorders, including hypertension. Cell culture and animal studies suggest that inorganic dietary nitrate may attenuate oxidative stress and inflammation through nitric oxide (NO), and there is a need to investigate whether this translates to humans. AIM: In this randomised, placebo-controlled crossover study, by measuring a combination of multiple blood biomarkers, we evaluated whether previously reported benefits of dietary nitrate translate to a reduced oxidative stress and an improved inflammation status in 15 men and women (age range: 56-71 years) with treated hypertension. METHODS: We investigated the effects of a single ∼400 mg-dose of nitrate at 3 h post-ingestion (3H POST) and the daily consumption of 2 × âˆ¼400 mg of nitrate over 4 weeks (4WK POST), through nitrate-rich versus nitrate-depleted (placebo) beetroot juice. Measurements included plasma nitrate and nitrite (NOx), oxidised low-density lipoprotein (oxLDL), F2-isoprostanes, protein carbonyls, oxidised (GSSG) and reduced glutathione (GSH); and serum high-sensitive C-reactive protein (hsCRP), chemokines, cytokines, and adhesion molecules. Flow cytometry was used to assess the relative proportion of blood monocyte subsets. RESULTS: At 4WK POST nitrate intervention, the oxLDL/NOx ratio decreased (mainly due to increases in plasma nitrate and nitrite) and the GSH/GSSG ratio (a sensitive biomarker for alterations in the redox status) increased, compared with placebo (for both ratios P < 0.01). The relative proportion of classical (CD14+CD16-) monocytes decreased at 4WK POST for placebo compared to nitrate intervention (P < 0.05). Other oxidative stress and inflammatory markers were not altered by increased nitrate intake relative to placebo. CONCLUSIONS: The data from this study point toward a subtle alteration in the redox balance toward a less pro-oxidative profile by a regular intake of inorganic nitrate from plant foods. CLINICAL TRIAL REGISTRY NUMBER: NCT04584372 (ClinicialTrials.gov).

17.
J Cancer Res Clin Oncol ; 150(7): 343, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38981922

RESUMO

PURPOSE: Radical resection of retroperitoneal liposarcoma (RLPS) may necessitate vascular resection and reconstruction. The study was conducted to assess surgical outcomes of surgery for RLPS with major vascular involvement. METHODS: Patients with RLPS who underwent surgical resection at the Sarcoma Center of Peking University Cancer Hospital between April 2011 and December 2022 were identified from a prospectively maintained database. Patients were classified into two groups: vascular resection and non-vascular resection groups. A propensity score matching analysis was performed to eliminate baseline differences between the groups. Surgical details and postoperative outcomes were analyzed. Furthermore, prognostic factors for local recurrence-free survival (LRFS) and overall survival (OS) were assessed. RESULTS: Overall, 199 patients were identified and the median follow-up period was 48 (interquartile range [IQR] 45-69) months. Vascular resection was performed in 42 (21%) patients, 25 of whom had vascular infiltration. A total of 39 patients had vascular replacement and 3 patients underwent partial resection (side-wall resection). Vascular resection was burdened by higher rates of major morbidity (38% vs. 14%, p < 0.001) and 30-day mortality (7.1% vs. 1.3%, p = 0.005). After propensity-matched analysis, patients who underwent vascular resection had 5-year LRFS and OS rates comparable to those without vascular involvement. Major vascular resection was not an independent risk factor for LRFS or OS. CONCLUSIONS: Although accompanied by increased risks of major morbidity and mortality, the major vascular resection enabled radical resection in patients with advanced RLPS, affording comparable 5-year LRFS and OS rates compared to those who did not.


Assuntos
Lipossarcoma , Pontuação de Propensão , Neoplasias Retroperitoneais , Humanos , Neoplasias Retroperitoneais/cirurgia , Neoplasias Retroperitoneais/patologia , Neoplasias Retroperitoneais/mortalidade , Masculino , Feminino , Lipossarcoma/cirurgia , Lipossarcoma/patologia , Lipossarcoma/mortalidade , Pessoa de Meia-Idade , Idoso , Procedimentos Cirúrgicos Vasculares/métodos , Adulto , Estudos Retrospectivos , Resultado do Tratamento , Prognóstico , Hospitais com Alto Volume de Atendimentos
18.
J Thorac Dis ; 16(6): 3782-3793, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38983151

RESUMO

Background: Nintedanib is a small molecule tyrosine kinase inhibitor (TKI) targeting vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), and fibroblast growth factor receptor (FGFR). The purpose of the study was to evaluate the response rate for patients with advanced non-small cell lung cancer (NSCLC) with mutations in TP53, VEGFR1-3, PDGFR-A, PDGFR-B, and FGFR1-3 treated with nintedanib as part of an open-label, single-arm pilot study. Methods: Patients with advanced NSCLC previously treated with platinum-doublet chemotherapy with the above mutations were enrolled. Exclusion criteria included necrotic tumors with invasion of blood vessels, history of recent thromboembolic events, increased risk of bleeding or thrombosis, myocardial infarction, and weight loss >10% within past 6 months. Nintedanib was administered at a dose of 200 mg orally twice daily until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Secondary endpoints included progression-free survival (PFS) and correlating outcomes with specific mutations. This study was registered with ClinicalTrials.gov, number NCT02299141. Results: Between 2015 and 2019, 20 patients were enrolled with a median age was 66 years, 15 (75%) were females, 15 (75%) had adenocarcinoma, and 17 patients had a TP53 mutation (85%). Seventeen (85%) had received prior immunotherapy and 11 (55%) had received at least three prior lines of systemic therapy. The ORR was 15% with three partial responses (PR), while 12 patients had stable disease (SD), with disease control rate (DCR) consisting of a PR and SD greater than or equal to 16 weeks of 65% (n=13). Median PFS was 4.3 months [95% confidence interval (CI): 1.8-7.9] and median overall survival (OS) was 11.3 months (95% CI: 3.5-44.2). Three patients experienced prolonged clinical benefit from nintedanib, remaining on treatment for over 1 year and all three had a TP53 mutation and received prior immunotherapy. The most common adverse events of any grade included nausea (80%), fatigue (70%), diarrhea (60%), and anorexia (60%). Conclusions: In this pilot study in heavily pretreated and molecularly selected patients with metastatic NSCLC, nintedanib showed modest activity.

19.
Radiol Case Rep ; 19(9): 3677-3682, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38983279

RESUMO

Vascular leiomyomas are infrequent benign soft tissue neoplasms arising from vascular wall. These lesions are more frequent in females, predominantly seen in lower extremities presenting as slowly enlarging freely mobile palpable soft tissue lesions, often painful. The role of imaging in small peripheral soft tissue masses is often limited to preoperative mapping with a long list of potential differentials. We are presenting 2 case studies of palpable masses with similar pathology, soft tissue vascular leiomyomas where its MR features can be helpful in inclusion of this entity not only in differential diagnosis of enhancing small peripheral soft tissue masses but can suggest a diagnosis in appropriate clinical scenario.

20.
World J Gastrointest Surg ; 16(6): 1548-1557, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38983331

RESUMO

BACKGROUND: Laparoscopic low anterior resection (LLAR) has become a mainstream surgical method for the treatment of colorectal cancer, which has shown many advantages in the aspects of surgical trauma and postoperative rehabilitation. However, the effect of surgery on patients' left coronary artery and its vascular reconstruction have not been deeply discussed. With the development of medical imaging technology, 3D vascular reconstruction has become an effective means to evaluate the curative effect of surgery. AIM: To investigate the clinical value of preoperative 3D vascular reconstruction in LLAR of rectal cancer with the left colic artery (LCA) preserved. METHODS: A retrospective cohort study was performed to analyze the clinical data of 146 patients who underwent LLAR for rectal cancer with LCA preservation from January to December 2023 in our hospital. All patients underwent LLAR of rectal cancer with the LCA preserved, and the intraoperative and postoperative data were complete. The patients were divided into a reconstruction group (72 patients) and a nonreconstruction group (74 patients) according to whether 3D vascular reconstruction was performed before surgery. The clinical features, operation conditions, complications, pathological results and postoperative recovery of the two groups were collected and compared. RESULTS: A total of 146 patients with rectal cancer were included in the study, including 72 patients in the reconstruction group and 74 patients in the nonreconstruction group. There were 47 males and 25 females in the reconstruction group, aged (59.75 ± 6.2) years, with a body mass index (BMI) (24.1 ± 2.2) kg/m2, and 51 males and 23 females in the nonreconstruction group, aged (58.77 ± 6.1) years, with a BMI (23.6 ± 2.7) kg/m2. There was no significant difference in the baseline data between the two groups (P > 0.05). In the submesenteric artery reconstruction group, 35 patients were type I, 25 patients were type II, 11 patients were type III, and 1 patient was type IV. There were 37 type I patients, 24 type II patients, 12 type III patients, and 1 type IV patient in the nonreconstruction group. There was no significant difference in arterial typing between the two groups (P > 0.05). The operation time of the reconstruction group was 162.2 ± 10.8 min, and that of the nonreconstruction group was 197.9 ± 19.1 min. Compared with that of the reconstruction group, the operation time of the two groups was shorter, and the difference was statistically significant (t = 13.840, P < 0.05). The amount of intraoperative blood loss was 30.4 ± 20.0 mL in the reconstruction group and 61.2 ± 26.4 mL in the nonreconstruction group. The amount of blood loss in the reconstruction group was less than that in the control group, and the difference was statistically significant (t = -7.930, P < 0.05). The rates of anastomotic leakage (1.4% vs 1.4%, P = 0.984), anastomotic hemorrhage (2.8% vs 4.1%, P = 0.672), and postoperative hospital stay (6.8 ± 0.7 d vs 7.0 ± 0.7 d, P = 0.141) were not significantly different between the two groups. CONCLUSION: Preoperative 3D vascular reconstruction technology can shorten the operation time and reduce the amount of intraoperative blood loss. Preoperative 3D vascular reconstruction is recommended to provide an intraoperative reference for laparoscopic low anterior resection with LCA preservation.

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