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Neutrophils play important roles in inflammatory airway diseases. In this study, we assessed whether apolipoprotein A-I modifies neutrophil heterogeneity as part of the mechanism by which it attenuates acute airway inflammation. Neutrophilic airway inflammation was induced by daily intranasal administration of LPS plus house dust mite (LPS+HDM) to Apoa1-/- and Apoa1+/+ mice for 3 d. Single-cell RNA sequencing was performed on cells recovered from bronchoalveolar lavage fluid on day 4. Unsupervised profiling identified 10 clusters of neutrophils in bronchoalveolar lavage fluid from Apoa1-/- and Apoa1+/+ mice. LPS+HDM-challenged Apoa1-/- mice had an increased proportion of the Neu4 neutrophil cluster that expressed S100a8, S100a9, and Mmp8 and had high maturation, aggregation, and TLR4 binding scores. There was also an increase in the Neu6 cluster of immature neutrophils, whereas neutrophil clusters expressing IFN-stimulated genes were decreased. An unsupervised trajectory analysis showed that Neu4 represented a distinct lineage in Apoa1-/- mice. LPS+HDM-challenged Apoa1-/- mice also had an increased proportion of recruited airspace macrophages, which was associated with a reciprocal reduction in resident airspace macrophages. Increased expression of a common set of proinflammatory genes, S100a8, S100a9, and Lcn2, was present in all neutrophils and airspace macrophages from LPS+HDM-challenged Apoa1-/- mice. These findings show that Apoa1-/- mice have increases in specific neutrophil and macrophage clusters in the lung during acute inflammation mediated by LPS+HDM, as well as enhanced expression of a common set of proinflammatory genes. This suggests that modifications in neutrophil and macrophage heterogeneity contribute to the mechanism by which apolipoprotein A-I attenuates acute airway inflammation.
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Apolipoproteína A-I , Ratones Noqueados , Neutrófilos , Neumonía , Animales , Ratones , Neutrófilos/inmunología , Neumonía/inmunología , Neumonía/genética , Apolipoproteína A-I/genética , Ratones Endogámicos C57BL , Lipopolisacáridos/inmunología , Líquido del Lavado Bronquioalveolar/inmunología , Líquido del Lavado Bronquioalveolar/citología , Pulmón/inmunología , Pulmón/patología , Calgranulina A , Calgranulina BRESUMEN
RATIONALE: Serum amyloid A (SAA) is bound to high-density lipoproteins (HDL) in blood. Although SAA is increased in the blood of patients with asthma, it is not known whether this modifies asthma severity. OBJECTIVE: We sought to define the clinical characteristics of patients with asthma who have high SAA levels and assess whether HDL from SAA-high patients with asthma is proinflammatory. METHODS: SAA levels in serum from subjects with and without asthma were quantified by ELISA. HDLs isolated from subjects with asthma and high SAA levels were used to stimulate human monocytes and were intravenously administered to BALB/c mice. RESULTS: An SAA level greater than or equal to 108.8 µg/mL was defined as the threshold to identify 11% of an asthmatic cohort (n = 146) as being SAA-high. SAA-high patients with asthma were characterized by increased serum C-reactive protein, IL-6, and TNF-α; older age; and an increased prevalence of obesity and severe asthma. HDL isolated from SAA-high patients with asthma (SAA-high HDL) had an increased content of SAA as compared with HDL from SAA-low patients with asthma and induced the secretion of IL-6, IL-1ß, and TNF-α from human monocytes via a formyl peptide receptor 2/ATP/P2X purinoceptor 7 axis. Intravenous administration to mice of SAA-high HDL, but not normal HDL, induced systemic inflammation and amplified allergen-induced neutrophilic airway inflammation and goblet cell metaplasia. CONCLUSIONS: SAA-high patients with asthma are characterized by systemic inflammation, older age, and an increased prevalence of obesity and severe asthma. HDL from SAA-high patients with asthma is proinflammatory and, when intravenously administered to mice, induces systemic inflammation, and amplifies allergen-induced neutrophilic airway inflammation. This suggests that systemic inflammation induced by SAA-high HDL may augment disease severity in asthma.
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Asma , Lipoproteínas HDL , Humanos , Animales , Ratones , Lipoproteínas HDL/metabolismo , Lipoproteínas HDL/farmacología , Proteína Amiloide A Sérica/análisis , Proteína Amiloide A Sérica/metabolismo , Proteína Amiloide A Sérica/farmacología , Factor de Necrosis Tumoral alfa/metabolismo , Interleucina-6 , Inflamación/metabolismo , Obesidad , AlérgenosRESUMEN
Objective To explore the feasibility and efficacy of the training program for aromatherapy in palliative care. Methods Data from four aromatherapy training programs held at Peking Union Medical College Hospital from 2016 to 2019 was collected.The feasibility and efficacy of the training were measured based on the self-reported questionnaires from 120 trainees. Results A total of 56 valid questionnaires were collected.The total score of the programs was 8.09.Trainees reported that the program enriched theoretical knowledge and enhanced practical confidence.After the training,79.6% of the trainees carried out aromatherapy in practice,while those who failed to practice were mainly due to the lack of appropriate opportunities.Some trainees suggested adding more practice hours and hoped to get follow-up guidance on a case-by-case basis. Conclusions It is feasible to carry out the short-term training program of aromatherapy in palliative care,which can enrich trainees' theoretical knowledge and enhance the practical confidence.It is necessary to provide continuous guidance after training to increase the proportion of trainees adopting aromatherapy in palliative care practice.
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Aromaterapia , Cuidados Paliativos , Humanos , Estudios de Factibilidad , Encuestas y CuestionariosRESUMEN
Objective To summarize the palliative care consultations proposed by the Emergency Department of Peking Union Medical College Hospital. Methods A retrospective study was conducted on 22 palliative care consultations in the Emergency Department of Peking Union Medical College Hospital from January 2017 to June 2020. Results A total of 18 patients (6 males and 12 females) received palliative care consultations in the Emergency Department,with the average age of (65±8) years (36-88 years).Specifically,10 and 6 patients received once and twice consultations,respectively,and 2 patients did not complete the consultation.Of the patients receiving palliative care consultations,15 had malignant tumors and 3 had non-neoplastic diseases.The reasons for palliative care consultations included communication (61.1%,11/18) and pain relief (61.1%,11/18).In terms of the place of death,8 patients died in the hospital and 6 patients in other medical institutions. Conclusion There is a clear demand for palliative care consultation in the Emergency Department of Peking Union Medical College Hospital,and the consultation can bring help to both emergency doctors and patients.
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Cuidados Paliativos , Derivación y Consulta , Masculino , Femenino , Humanos , Persona de Mediana Edad , Anciano , Cuidados Paliativos/métodos , Estudios Retrospectivos , Hospitales , Servicio de Urgencia en HospitalRESUMEN
Objective To explore the effects of palliative care consultation on medical professionals who have requested it in Peking Union Medical College Hospital. Methods Semi-structured interviews were conducted with 17 medical professionals who had requested palliative care consultation.Results Palliative care consultation had the following positive effects:building a bridge for doctor-patient communication,providing psychological support to reduce the sense of occupational exhaustion for medical professionals,providing technical support for medical professionals to help patients relieve symptoms,helping medical professionals in the multidisciplinary learning of palliative care,adding humanistic care and neglected ethical concerns.Conclusion Palliative care consultation improves the quality of care for dying patients,and the capacity of consultation needs to be enhanced urgently.
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Cuidados Paliativos , Derivación y Consulta , Hospitales , Humanos , Investigación CualitativaRESUMEN
The primary function of APOE (apolipoprotein E) is to mediate the transport of cholesterol- and lipid-containing lipoprotein particles into cells by receptor-mediated endocytosis. APOE also has pro- and antiinflammatory effects, which are both context and concentration dependent. For example, Apoe-/- mice exhibit enhanced airway remodeling and hyperreactivity in experimental asthma, whereas increased APOE levels in lung epithelial lining fluid induce IL-1ß secretion from human asthmatic alveolar macrophages. However, APOE-mediated airway epithelial cell inflammatory responses and signaling pathways have not been defined. Here, RNA sequencing of human asthmatic bronchial brushing cells stimulated with APOE identified increased expression of mRNA transcripts encoding multiple proinflammatory genes, including CXCL5 (C-X-C motif chemokine ligand 5), an epithelial-derived chemokine that promotes neutrophil activation and chemotaxis. We subsequently characterized the APOE signaling pathway that induces CXCL5 secretion by human asthmatic small airway epithelial cells (SAECs). Neutralizing antibodies directed against TLR4 (Toll-like receptor 4), but not TLR2, attenuated APOE-mediated CXCL5 secretion by human asthmatic SAECs. Inhibition of TAK1 (transforming growth factor-ß-activated kinase 1), IκKß (inhibitor of nuclear factor κ B kinase subunit ß), TPL2 (tumor progression locus 2), and JNK (c-Jun N-terminal kinase), but not p38 MAPK (mitogen-activated protein kinase) or MEK1/2 (MAPK kinase 1/2), attenuated APOE-mediated CXCL5 secretion. The roles of TAK1, IκKß, TPL2, and JNK in APOE-mediated CXCL5 secretion were verified by RNA interference. Furthermore, RNA interference showed that after APOE stimulation, both NF-κB p65 and TPL2 were downstream of TAK1 and IκKß, whereas JNK was downstream of TPL2. In summary, elevated levels of APOE in the airway may activate a TLR4/TAK1/IκKß/NF-κB/TPL2/JNK signaling pathway that induces CXCL5 secretion by human asthmatic SAECs. These findings identify new roles for TLR4 and TPL2 in APOE-mediated proinflammatory responses in asthma.
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Apolipoproteínas E/metabolismo , Asma/metabolismo , Quimiocina CXCL5/metabolismo , Células Epiteliales/metabolismo , Sistema Respiratorio/metabolismo , Transducción de Señal/fisiología , Receptor Toll-Like 4/metabolismo , Quimiocinas/metabolismo , Humanos , Inflamación/metabolismo , Neutrófilos/metabolismo , ARN Mensajero/metabolismoRESUMEN
BRAFV600E mutation is frequently observed in melanoma, and contributes to tumor malignancy. Despite inhibition of BRAF causes a profound cell growth inhibition and a strong clinical benefit in BRAFV600E melanoma, acquired drug resistance is still the major hurdle. In this study, we demonstrate that BRAFV600E drives cell growth and glycolysis in melanoma cells but does so by a previously unappreciated mechanism that involves direct induction of Skp2. Skp2 is highly expressed in melanoma tissues and particularly in tissues with BRAFV600E mutation. The inhibition of BRAFV600E by either siRNA or inhibitor vemurafenib suppressed Skp2 expression and cell growth. Mechanistic study shows that BRAFV600E suppression of Skp2 is dependent on c-Myc transcription factor via specifically bounding to the E-box region on SKP2 promoter. Further, the overexpression of Skp2 resulted in a markedly increase in cell growth, cell cycle progression and glycolysis which were repressed by BRAFV600E inhibition. Supporting the biological significance, Skp2 is specifically correlated with poor patient outcome in BRAFV600E but did not in BRAFWT melanomas. Thus, as a downstream target of BRAFV600E, Skp2 is critical for responses to BRAF inhibition, indicating targeting Skp2 might be a promising strategy for the treatment of BRAFi resistant melanomas.
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Melanoma/metabolismo , Inhibidores de Proteínas Quinasas/química , Proteínas Proto-Oncogénicas B-raf/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-myc/metabolismo , Proteínas Quinasas Asociadas a Fase-S/metabolismo , Vemurafenib/química , Línea Celular Tumoral , Proliferación Celular , Supervivencia Celular/genética , Resistencia a Antineoplásicos/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica , Humanos , Mutación , Inhibidores de Proteínas Quinasas/metabolismo , Proteínas Proto-Oncogénicas B-raf/genética , ARN Interferente Pequeño/metabolismo , Vemurafenib/metabolismoRESUMEN
BACKGROUND: Low-density lipoprotein receptor-related protein 1 (LRP-1) is a scavenger receptor that regulates adaptive immunity and inflammation. LRP-1 is not known to modulate the pathogenesis of allergic asthma. OBJECTIVE: We sought to assess whether LRP-1 expression by dendritic cells (DCs) modulates adaptive immune responses in patients with house dust mite (HDM)-induced airways disease. METHODS: LRP-1 expression on peripheral blood DCs was quantified by using flow cytometry. The role of LRP-1 in modulating HDM-induced airways disease was assessed in mice with deletion of LRP-1 in CD11c+ cells (Lrp1fl/fl; CD11c-Cre) and by adoptive transfer of HDM-pulsed CD11b+ DCs from Lrp1fl/fl; CD11c-Cre mice to wild-type (WT) mice. RESULTS: Human peripheral blood myeloid DC subsets from patients with eosinophilic asthma have lower LRP-1 expression than cells from healthy nonasthmatic subjects. Similarly, LRP-1 expression by CD11b+ lung DCs was significantly reduced in HDM-challenged WT mice. HDM-challenged Lrp1fl/fl; CD11c-Cre mice have a phenotype of increased eosinophilic airway inflammation, allergic sensitization, TH2 cytokine production, and mucous cell metaplasia. The adoptive transfer of HDM-pulsed LRP-1-deficient CD11b+ DCs into WT mice generated a similar phenotype of enhanced eosinophilic inflammation and allergic sensitization. Furthermore, CD11b+ DCs in the lungs of Lrp1fl/fl; CD11c-Cre mice have an increased ability to take up HDM antigen, whereas bone marrow-derived DCs display enhanced antigen presentation capabilities. CONCLUSION: This identifies a novel role for LRP-1 as a negative regulator of DC-mediated adaptive immune responses in the setting of HDM-induced eosinophilic airway inflammation. Furthermore, the reduced LRP-1 expression by circulating myeloid DCs in patients with eosinophilic asthma suggests a possible role for LRP-1 in modulating type 2-high asthma.
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Asma/inmunología , Células Dendríticas/inmunología , Dermatophagoides pteronyssinus/inmunología , Eosinofilia/inmunología , Proteína 1 Relacionada con Receptor de Lipoproteína de Baja Densidad/inmunología , Inmunidad Adaptativa , Adulto , Alérgenos/inmunología , Animales , Antígenos Dermatofagoides/inmunología , Asma/sangre , Asma/fisiopatología , Líquido del Lavado Bronquioalveolar/citología , Eosinofilia/sangre , Eosinofilia/fisiopatología , Femenino , Humanos , Inmunoglobulina E/sangre , Inmunoglobulina G/sangre , Masculino , Ratones Transgénicos , Persona de Mediana EdadRESUMEN
Oncogenic c-Myc-induced metabolic reprogramming triggers cellular dependency on exogenous glucose and glutamine. Understanding how nutrients are used may provide new target for therapeutic intervention. We previously provided an alternate route to c-Myc-driven glucose metabolism via the repression of thioredoxin-interacting protein (TXNIP), which is a potent negative regulator of glucose uptake. Herein, we demonstrate that c-Myc suppression of TXNIP is predominantly through the activation of glutaminolysis via glutaminase (GLS1) in prostate cancer cells. Glutamine depletion blocked c-Myc-dependent reductions of TXNIP and its principal regulator MondoA transcriptional activity. Further, GLS1 inhibition by either siRNA or CB-839 resumed TXNIP expression that was repressed by c-Myc. The TXNIP promoter with mutant E-Box region, which was recognized by MondoA, failed to respond to c-Myc or GLS1, indicating c-Myc repression of TXNIP by GLS1 is predominantly through the blockage of MondoA activity. Especially, ectopic TXNIP expression decreased c-Myc-induce glucose uptake and lead to a broad range of glycolytic target gene suppressions. Thus TXNIP is a key adaptor for c-Myc-driven aerobic glycolysis. Supporting the biological significance of c-Myc and TXNIP, their reciprocal relationship are correlates with patient outcome and contributes to the aggressive phenotype in PCAs.
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Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/metabolismo , Proteínas Portadoras/metabolismo , Glutaminasa/metabolismo , Glucólisis , Neoplasias de la Próstata/metabolismo , Proteínas Proto-Oncogénicas c-myc/metabolismo , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Ácidos Cetoglutáricos/metabolismo , Masculino , Fenotipo , Análisis de Componente Principal , Hiperplasia Prostática/metabolismoRESUMEN
Objective s The in-hosptial palliative care consultation (PCC) is emerging as a routine service in some medical center in China. The current study evaluated how physicians in primary care team and consultation team perceive the PCC service for the purpose of investigating the effectiveness of this consultation model in a general hospital. Methods In-hosptial palliative care consultations have been carried out at Peking Union Medical College Hosptial by a dedicated consultation team, and 37 consultations were completed in 2016. A questionnaire was designed for physicians in terms of its benefits to patients,their family as well as the primary care team. Physicians who applied for consultation in 2016 formally (requested from the department other than the Geriatrics) and informally (by rotating residents and unemployed visiting doctors in geriatric department) were invited to participate in the survey by scanning a two dimentional code on social networking platform. Results There were 103 physicians participated in the survey, including primary care physicians from the department of Internal Medicine (n=8), Gynaecology (n=16) and Surgery (n=13), rotating residents (n=30), visiting doctors (n=16) in Geriatric department, and PCC team members (n=20). 94.0% of the non-PCC physicians agreed that PCC relieved the suffering of patients; 89.2% thought PCC improved the quality of patients' life; there were 91.6%, 95.2%, 90.4% physicians who felt it relieved the anxiety of patients, of family members and of care providers, respectively. There were 96.4% physicians who felt it could ease the tension in physician-patient relationship; 97.6% felt it lower the risk for medical negligence, and 96.4% of doctors who applied for PPC felt satisfied with PCC service in terms of process and achieving objectives of consultation. More primary-team physician agree "PCC service helps the physicians better understand palliative care" than PCC members (97.6% vs. 80%, P<0.05), while both were interested in learning more on palliative medicine (100% vs. 96.4%, P>0.05). Conclusion Palliative care consultation service in a general hospital is efficacious and acclaimed.The primary care physicians and the PCC members hold positive attitudes to the benefits that the PCC services bring to patients, family members, and physicians themselves. PCC for terminal patients in a general hospital may serve as a good modle for promotion of palliative care in China.
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Cuidados Paliativos/organización & administración , Médicos/psicología , China , Hospitales Generales , Humanos , Derivación y Consulta , Encuestas y CuestionariosRESUMEN
Objective To analyzed the current situations and needs of the continuing education on hospice and palliative care (HPC) in China based on the response from trainees in the 2016 National Hospice and Palliative Medicine Training Program. Methods A questionnaire-based survey was performed among 141 trainees who attended the program held by Peking Union Medical College Hospital in 2016. The questionnaire items included the awareness and knowledge of HPC,learning Objective s,learning gains,and future plans. Results The trainees came from 19 provinces and municipalities. Their professions included doctors (66.0%),nurses (17.0%),physical therapists (1.4%),psychologists (5.0%),social workers (2.1%),volunteers (6.4%) and hospital managers (2.1%). Doctors'disciplines included geriatrics (56.0%),medical oncology (11.8%),and others (32.2%). Among these 141 participants,111 (78.7%) had not attended any HPC course before,134 (95.0%) were aware of HPC,and 131 (92.9%) needed help from others when providing care for terminally-ill patients. The median score for symptom control and communication skills among 141 trainees were 3.0(2.0,4.0) points and 1.0(0.0,2.0) points,respectively. The average score of the final examination involving case analysis and medical knowledge of symptom control was (59.1±18.0)scores (centesimal system). Finally,136 trainees (96.5%) were willing to receive further training on HPC. Conclusion It is important to do more HPC education and training among medical staff,so as to strengthen their knowledge and capability in symptom control,communication,and evaluation of death quality.
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Educación Médica Continua , Educación Continua en Enfermería , Hospitales para Enfermos Terminales , Cuidados Paliativos , China , Humanos , Encuestas y CuestionariosRESUMEN
The very low density lipoprotein receptor (VLDLR) is a member of the low-density lipoprotein receptor family that binds multiple ligands and plays a key role in brain development. Although the VLDLR mediates pleiotropic biological processes, only a limited amount of information is available regarding its role in adaptive immunity. In this study, we identify an important role for the VLDLR in attenuating house dust mite (HDM)-induced airway inflammation in experimental murine asthma. We show that HDM-challenged Vldlr(-/-) mice have augmented eosinophilic and lymphocytic airway inflammation with increases in Th2 cytokines, C-C chemokines, IgE production, and mucous cell metaplasia. A genome-wide analysis of the lung transcriptome identified that mRNA levels of CD209e (DC-SIGNR4), a murine homolog of DC-SIGN, were increased in the lungs of HDM-challenged Vldlr(-/-) mice, which suggested that the VLDLR might modify dendritic cell (DC) function. Consistent with this, VLDLR expression by human monocyte-derived DCs was increased by HDM stimulation. In addition, 55% of peripheral blood CD11c(+) DCs from individuals with allergy expressed VLDLR under basal conditions. Lastly, the adoptive transfer of HDM-pulsed, CD11c(+) bone marrow-derived DCs (BMDCs) from Vldlr(-/-) mice to the airways of wild type recipient mice induced augmented eosinophilic and lymphocytic airway inflammation upon HDM challenge with increases in Th2 cytokines, C-C chemokines, IgE production, and mucous cell metaplasia, as compared with the adoptive transfer of HDM-pulsed, CD11c(+) BMDCs from wild type mice. Collectively, these results identify a novel role for the VLDLR as a negative regulator of DC-mediated adaptive immune responses in HDM-induced allergic airway inflammation.
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Inmunidad Adaptativa , Células Dendríticas/inmunología , Pyroglyphidae , Receptores de LDL/inmunología , Hipersensibilidad Respiratoria/inmunología , Animales , Antígeno CD11c/genética , Antígeno CD11c/inmunología , Moléculas de Adhesión Celular/genética , Moléculas de Adhesión Celular/inmunología , Citocinas/genética , Citocinas/inmunología , Células Dendríticas/patología , Eosinófilos/inmunología , Eosinófilos/patología , Femenino , Estudio de Asociación del Genoma Completo , Humanos , Inmunoglobulina E/genética , Inmunoglobulina E/inmunología , Lectinas Tipo C/genética , Lectinas Tipo C/inmunología , Masculino , Ratones , Ratones Noqueados , Receptores de Superficie Celular/genética , Receptores de Superficie Celular/inmunología , Receptores de LDL/genética , Hipersensibilidad Respiratoria/genética , Hipersensibilidad Respiratoria/patología , Células Th2/inmunología , Células Th2/patologíaRESUMEN
Many neuropeptides are members of peptide families, with multiple structurally similar isoforms frequently found even within a single species. This raises the question of whether the individual peptides serve common or distinct functions. In the accompanying paper, we found high isoform specificity in the responses of the lobster (Homarus americanus) cardiac neuromuscular system to members of the pyrokinin peptide family: only one of five crustacean isoforms showed any bioactivity in the cardiac system. Because previous studies in other species had found little isoform specificity in pyrokinin actions, we examined the effects of the same five crustacean pyrokinins on the lobster stomatogastric nervous system (STNS). In contrast to our findings in the cardiac system, the effects of the five pyrokinin isoforms on the STNS were indistinguishable: they all activated or enhanced the gastric mill motor pattern, but did not alter the pyloric pattern. These results, in combination with those from the cardiac ganglion, suggest that members of a peptide family in the same species can be both isoform specific and highly promiscuous in their modulatory capacity. The mechanisms that underlie these differences in specificity have not yet been elucidated; one possible explanation, which has yet to be tested, is the presence and differential distribution of multiple receptors for members of this peptide family.
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Nephropidae/efectos de los fármacos , Sistema Nervioso/efectos de los fármacos , Neuropéptidos/farmacología , Isoformas de Proteínas , Animales , Sistema Digestivo/efectos de los fármacos , Sistema Digestivo/inervación , Ganglios de Invertebrados/efectos de los fármacos , Ganglios de Invertebrados/fisiología , Contracción Muscular/efectos de los fármacos , Nephropidae/fisiología , Isoformas de Proteínas/farmacologíaRESUMEN
Apolipoprotein A-I (apoA-I) is an important component of high-density lipoprotein particles that mediates reverse cholesterol transport out of cells by interacting with the ATP-binding cassette transporter 1 (ABCA1). apoA-I has also been shown to attenuate neutrophilic airway inflammation in experimental ovalbumin (OVA)-induced asthma by reducing the expression of granulocyte colony-stimulating factor (G-CSF). Here, we hypothesized that overexpression of the ABCA1 transporter might similarly attenuate OVA-induced neutrophilic airway inflammation. Tie2-human ABCA1 (hABCA1) mice expressing human ABCA1 under the control of the Tie2 promoter, which is primarily expressed by vascular endothelial cells, but can also be expressed by macrophages, received daily intranasal OVA challenges, 5 d/wk for 5 weeks. OVA-challenged Tie2-hABCA1 mice had significant reductions in total bronchoalveolar lavage fluid (BALF) cells that reflected a decrease in neutrophils, as well as reductions in peribronchial inflammation, OVA-specific IgE levels, and airway epithelial thickness. The reduced airway neutrophilia in OVA-challenged Tie2-hABCA1 mice was associated with significant decreases in G-CSF protein levels in pulmonary vascular endothelial cells, alveolar macrophages, and BALF. Intranasal administration of recombinant murine G-CSF to OVA-challenged Tie2-hABCA1 mice for 5 days increased BALF neutrophils to a level comparable to that of OVA-challenged wild-type mice. We conclude that ABCA1 suppresses OVA-induced airway neutrophilia by reducing G-CSF production by vascular endothelial cells and alveolar macrophages. These findings suggest that ABCA1 expressed by vascular endothelial cells and alveolar macrophages may play important roles in attenuating the severity of neutrophilic airway inflammation in asthma.
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Transportador 1 de Casete de Unión a ATP/genética , Transportador 1 de Casete de Unión a ATP/inmunología , Neutrófilos/inmunología , Neumonía/inmunología , Animales , Asma/inmunología , Líquido del Lavado Bronquioalveolar/inmunología , Colesterol/inmunología , Células Endoteliales/inmunología , Factor Estimulante de Colonias de Granulocitos/genética , Humanos , Macrófagos Alveolares/inmunología , Ratones Endogámicos C57BL , Ratones Transgénicos , Ovalbúmina/inmunología , Ovalbúmina/farmacología , Neumonía/inducido químicamente , Regiones Promotoras Genéticas/genética , Receptor TIE-2/genéticaRESUMEN
Transposable elements (TEs) represent almost half of the human genome. Historically deemed 'junk DNA', recent technological advancements have stimulated a wave of research into the functional impact of TEs on gene-regulatory networks in evolution and development, as well as in diseases including cancer. The genetic and epigenetic evolution of cancer involves the exploitation of TEs, whereby TEs contribute directly to cancer-specific gene activities. This Review provides a perspective on the role of TEs in cancer as being a 'double-edged sword', both promoting cancer evolution and representing a vulnerability that could be exploited in cancer therapy. We discuss how TEs affect transcriptome regulation and other cellular processes in cancer. We highlight the potential of TEs as therapeutic targets for cancer. We also summarize technical hurdles in the characterization of TEs with genomic assays. Last, we outline open questions and exciting future research avenues.
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Elementos Transponibles de ADN , Neoplasias , Humanos , Elementos Transponibles de ADN/genética , Redes Reguladoras de Genes , Genoma Humano , Oncogenes , Evolución Molecular , Neoplasias/genética , Neoplasias/terapiaRESUMEN
This case study highlights a 79-year-old man with chronic low back pain attributed to severe lumbar scoliosis. Physical examination revealed the unilateral absence of pectoral muscles and ipsilateral hand anomalies, indicative of Poland syndrome (PS). The patient also experienced depression due to chronic pain and PS-related anomalies. A multi-disciplinary approach proved effective in alleviating both pain and depression.
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[This corrects the article DOI: 10.7759/cureus.62300.].
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Background The prevalence of obesity in combination with sarcopenia, the age-related loss of muscle mass and strength or physical function, is on the rise among adults aged 65 years and older. A significant portion of this demographic now falls under the classification of sarcopenic obesity, a high-risk geriatric syndrome predominantly seen in an aging population vulnerable to compounded complications from both sarcopenia and obesity. It is essential to promptly evaluate the impact of academic research in this field, taking into account factors such as geographical regions, authors, journals, and institutions. Furthermore, exploring current topics and identifying potential areas that could inspire future researchers to conduct additional studies is crucial for advancing overall health in this population. Methodology A search was conducted in the Web of Science Core Collection database to identify English language articles and reviews focusing on sarcopenic obesity in older adults, published between January 1, 2004, and December 31, 2023. Bibliometric analysis was performed using VOSviewer (v.1.6.18) and CiteSpace (v.6.1.R2). Results A total of 985 original English-language articles were collected, consisting of 783 articles and 202 reviews. The volume of research publications in this field has shown significant growth since 2012. The United States leads in contributions, with 239 articles (24.3% of the total) and the highest number of citations at 18,403, along with the highest total link strength. The University of Melbourne in Australia stands out with 25 published articles (2.5% of the total). University of Verona in Italy has the most citations at 9,405, and Monash University in Australia has the highest total link strength at 53. Among prolific authors, John A. Batsis from Duke University is the most productive with 24 articles (2.4% of the total). The journal "Nutrients" has the most articles on sarcopenic obesity in older adults, publishing 54 articles (5.5% of the total). Key topics in this area include sarcopenia, obesity, sarcopenic obesity, and elderly. Recent interventions focus on "nutrition" and "exercise" for sarcopenic obesity in older adults. Conclusions Research on sarcopenic obesity in older adults has seen significant growth on a global scale from 2004 to 2023, indicating a promising area for further study with potential benefits from current advancements. Although academic inquiries have shed light on various aspects of sarcopenic obesity in older adults, there remains a noticeable dearth of clinical research and evidence-based medicine on the effective management of this condition in elderly individuals. Future studies could focus on developing tailored interventions for older adults with sarcopenic obesity.
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Sarcopenic obesity, characterized by both obesity and sarcopenia, significantly impacts health and independence of affected individuals. There is an urgent need to explore effective strategies for addressing or preventing sarcopenic obesity. An initial critical step is to promptly assess the impact of academic research in this field, considering factors such as geographical regions, authors, journals, and institutions. It is also essential to analyze current trends and identify potential areas that may inspire future researchers to conduct further studies, ultimately improving public health outcomes for individuals with sarcopenic obesity. To achieve this, bibliometric research was conducted using the Web of Science Core Collection database to identify English language articles and reviews focusing on sarcopenic obesity interventions published between January 1, 2004, and June 15, 2024, followed by a literature review. A total of 929 English-language articles were collected, consisting of 645 research articles and 284 reviews. Research output in the field has shown significant growth since 2017, reaching a peak of 139 papers in 2022. The United States leads in publication output with 234 papers and a total of 13,971 citations, highlighting substantial international collaboration. Both the United States and Europe are recognized as key academic hubs for sarcopenic obesity intervention research, characterized by robust academic interactions. Moreover, there has been a notable increase in publication volume from China, South Korea, and Japan. Noteworthy authors in this field include Boirie Y from Université Clermont Auvergne in France, Prado CM from the University of Alberta in Canada, Cruz-Jentoft AJ from Hospital Universitario Ramon y Cajal in Spain, and Prado CM from the University of Alberta, known for their high citation count. The University of Alberta leads in the number of publications, while the University of Verona in Italy leads in citation frequency. Journals with higher publication volumes in sarcopenic obesity intervention include Nutrients, Clinical Nutrition, and Journal of Cachexia Sarcopenia and Muscle. Among the top 20 keywords, the most relevant interventions for sarcopenic obesity are exercise, nutrition, resistance training, physical activity, and muscle strength. The primary evidence currently available suggests that resistance training is the most effective method for enhancing muscle strength in sarcopenic obesity patients. Additionally, combining protein supplementation with resistance exercise has shown encouraging results in reducing fat mass in these individuals. To progress in this field, it is crucial to foster collaboration among countries, regions, and academic institutions, promoting multidisciplinary partnerships.
RESUMEN
Cushing's disease (CD) is a rare and serious condition characterized by a persistent increase in cortisol levels, resulting in various complications across multiple bodily systems. Elderly individuals often face a multitude of chronic illnesses and geriatric syndromes, which can complicate the diagnosis and treatment of CD in this demographic. This case study details the presentation of an elderly patient with adrenocorticotropic hormone (ACTH)-dependent CD, who initially presented with an acute exacerbation of chronic obstructive pulmonary disease. The article delves into the unique onset characteristics and treatment strategies for CD in the elderly, providing valuable insights for the comprehensive management of similar clinical cases.