Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 49
Filtrar
Más filtros

Banco de datos
País/Región como asunto
Tipo del documento
Intervalo de año de publicación
1.
Thromb J ; 22(1): 58, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38982506

RESUMEN

BACKGROUND: Mechanical thrombectomy (MT) has become the mainstay of treatment for acute ischemic stroke (AIS) recently. This case-control study aimed to identify the pivotal role of inflammation in the prognosis of AIS patients after MT. METHODS: Altogether, 70 AIS patients who underwent MT were retrospectively recruited for this study. Receiver operating characteristic analysis was performed to demonstrate the sensitivity and specificity of the inflammatory variables for predicting prognosis. A meta-analysis was performed to pool the published results together. Stata software was used for analysis. RESULTS: There was no differences in pre-MT inflammatory biomarkers between patients who survived and those who died, as well as patients with modified Rankin Scale (mRS) 0-2 and mRS ≥ 3. In contrast, post-MT C-reactive protein (CRP) levels might be a potential parameter to predict death after thrombectomy [area under the curve (AUC), 95%confidence interval (CI), 0.737, 0.587-0.887; p = 0.005; optimal cutoff value = 4.565]. Moreover, post-MT monocyte count might be an appropriate parameter to predict poor long-term prognosis after thrombectomy (AUC, 95%CI, 0.704, 0.575-0.833; p = 0.017; optimal cutoff value = 0.345). A meta-analysis revealed that the pre-MT inflammatory indices, including white blood cell count (weighted mean difference, 95%CI, 1.32, 1.01-1.63), neutrophil count (1.23, 0.95-1.51), monocyte count (0.05, 0.02-0.09), neuthrophil-to-lymphocyte ratio (2.42, 1.98-2.87) and platelet-to-lymphocyte ratio (24.65, 7.99-41.32), were higher in patients with 3-month mRS ≥ 3, and the lymphocyte count (-0.31,-0.43 to -0.18) was lower in this cohort. CONCLUSIONS: Inflammatory indices were significantly associated with the prognosis of patients undergoing MT, especially post-MT CRP and monocyte count, which can predict long-term outcomes.

2.
BMC Psychiatry ; 24(1): 124, 2024 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-38355472

RESUMEN

BACKGROUND: This study examined the association between social support and the severity of positive symptoms in rural community-dwelling schizophrenia patients during the COVID-19 pandemic. METHOD: The cross-sectional study included 665 rural community-dwelling schizophrenia patients investigated during the COVID-19 pandemic. Social support was measured using the Social Support Rating Scale, and positive symptoms were assessed using the Positive Scale extracted from the Positive and Negative Syndrome Scale. Multiple linear regression was adopted to examine the association of social support with positive symptoms. RESULT: The scores for total social support, subjective support, objective support and the use of social support were 28.3 ± 5.9, 16.4 ± 5.2, 6.5 ± 1.4 and 5.4 ± 2.8, respectively. Total social support (ß = -0.08, 95%CI: -0.13 to -0.02, P < 0.01) and subjective social support (ß = -0.10, 95%CI: -0.16 to -0.04, P < 0.01) were significantly and negatively associated with the Positive Scale score after adjustment for confounders. Objective social support (ß = 0.11, 95%CI: -0.10 to 0.32, P = 0.31) and the use of social support (ß = -0.03, 95%CI: -0.14 to 0.07, P = 0.53) were not significantly associated with the Positive Scale score. CONCLUSION: The study confirmed the importance of social support, especially subjective support, provided to rural community-dwelling schizophrenia patients during the COVID-19 pandemic. This support should be addressed and strengthened for such patients in emergent events.


Asunto(s)
COVID-19 , Esquizofrenia , Humanos , Vida Independiente , Esquizofrenia/epidemiología , Estudios Transversales , Pandemias , Apoyo Social
3.
Thromb J ; 21(1): 82, 2023 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-37525162

RESUMEN

BACKGROUND: Venous thromboembolism (VTE) is a common thrombotic vascular disease that has a significant impact on people's well-being and quality of life. A plethora of clinical studies explore the relationship between inflammatory biomarkers and VTE but yield conflicting results. This article proposed to pool these studies to draw a more convincing conclusion. METHODS: We searched several databases for studies before April 2023. Available data was processed using Stata software (version 15.0 SE) and R (version 4.1.2). This meta-analysis has been registered in PROSPERO (CRD42022321815). The VTE in this review encompassed pulmonary embolism, deep vein thrombosis, and cerebral venous thrombosis. RESULTS: A total of 25 articles were finally involved in this study. Our results revealed that higher levels of high-sensitivity C-reactive protein (hs-CRP, MD, 0.63, 95%CI, 0.21-1.05) and C-reactive protein (CRP)> 3ug/ml (OR, 1.52, 95%CI, 1.18-1.96) might be regarded as risk factors for future VTE occurrence. The elevated levels of monocyte (MD, 0.03, 95%CI, 0.00-0.05), hs-CRP (0.85, 0.61-1.08), CRP (0.66, 0.20-1.13) and IL-6 (0.47, 0.25-0.70) might represent the previous VTE; a series of markers such as white blood cell (1.43, 0.88-1.98), neutrophil (1.79, 1.02-2.56), monocyte (0.17, 0.14-0.21), hs-CRP (3.72, 1.45-5.99), IL-6 (5.99, 4.52-7.46), platelet-lymphocyte ratio (33.1, 24.45-41.78) and neutrophil-lymphocyte ratio (1.34, 0.95-1.73) increased during the acute phase of VTE. CONCLUSIONS: In general, activated inflammatory biomarkers might not only be correlated with an increased risk of VTE, but may also give a hint of the occurrence of VTE in clinical settings.

4.
J Med Internet Res ; 25: e43532, 2023 01 17.
Artículo en Inglés | MEDLINE | ID: mdl-36649059

RESUMEN

BACKGROUND: The minority stress model postulates that men who have sex with men (MSM) often encounter multiple stressors because of their sexual minority status, which may lead to psychological problems and maladaptive coping such as addictive behaviors (eg, internet gaming disorder [IGD]). It was hypothesized that hopelessness and loneliness would be associated with IGD via self-control among MSM. OBJECTIVE: This study investigated the prevalence of IGD and its associations with variables related to minority stress (loneliness and hopelessness) among MSM who were university students. Mediation involving such associations via self-control was also explored. METHODS: With informed consent, 305 MSM attending universities in Sichuan, China participated in the study. The validated Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) checklist was used to assess IGD. Multivariable logistic regression adjusted for background factors and structural equation modeling were conducted. RESULTS: The prevalence of IGD was 12.8% (n=39). Logistic regression found that IGD was positively associated with hopelessness and loneliness, and negatively associated with self-control. The structural equation modeling identified three significant paths between hopelessness/loneliness and IGD: (1) hopelessness → lower self-control → higher IGD (full mediation), (2) loneliness → lower self-control → higher IGD (partial mediation: effect size of 28%), and (3) a direct effect from loneliness to IGD. CONCLUSIONS: IGD was prevalent among young MSM and warrants interventions that may try to reduce the level of psychosocial problems such as loneliness and hopelessness and improve self-control. According to the socioecological model, the promotion of social acceptance and reduction in stigma toward MSM are important in reducing loneliness and hopefulness among MSM. Self-control links up the relationships between psychosocial problems and IGD and should be given special attention. Longitudinal studies are warranted to confirm the findings and test new mediations between loneliness/hopelessness and MSM with IGD.


Asunto(s)
Conducta Adictiva , Minorías Sexuales y de Género , Juegos de Video , Masculino , Humanos , Femenino , Homosexualidad Masculina/psicología , Universidades , Soledad/psicología , Estudios Transversales , Trastorno de Adicción a Internet/epidemiología , Estudiantes/psicología , Internet , Juegos de Video/psicología , Conducta Adictiva/psicología
5.
Eur J Cancer Care (Engl) ; 31(1): e13547, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34918408

RESUMEN

OBJECTIVE: To investigate the prevalence of cancer-related fatigue (CRF) in patients with lymphoma and to explore the burden of CRF on the family caregivers (FCs). METHODS: A cross-sectional study was conducted in a university-affiliated tertiary care hospital in China. Patients with lymphoma who received treatment in the in-patient ward of the Haematology Department were consecutively recruited. Face-to-face interviews were conducted to gather information related to the patients' sociodemographic characteristics and perceived CRF and its burden on the FCs. Cochran-Armitage trend analysis and Multivariable logistic regression analyses were employed to determine the association between CRF and the FCs' burden. RESULTS: Of the 116 cancer patient-FC dyads, about 70% of patients experienced some level of fatigue, while 51% of unpaid family members suffered some degree of depression. The Cochran-Armitage trend analysis showed that the FCs' burden significantly increased with the severity of CRF. Logistic regression indicated that the FCs of the patients reporting fatigue experienced a higher burden in both the unadjusted and adjusted models. CONCLUSION: The prevalence of CRF appeared to be high among patients with lymphoma. It might be important to design innovative health-promoting practices for ameliorating or preventing the impact of fatigue.


Asunto(s)
Linfoma , Neoplasias , Cuidadores , Estudios Transversales , Fatiga/epidemiología , Fatiga/etiología , Humanos , Linfoma/complicaciones , Linfoma/epidemiología , Neoplasias/complicaciones , Calidad de Vida
6.
Int J Hyperthermia ; 34(8): 1311-1315, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-29301450

RESUMEN

OBJECTIVE: To investigate the effects of a microbubble ultrasound contrast agent on high-intensity focused ultrasound (HIFU) treatment of uterine fibroids. METHODS: A total of 120 patients with solitary uterine fibroid were randomly assigned into Groups A, B, C and D. Patients in Groups A and B received 1.5 ml of SonoVue, Groups C and D received 1.5 ml of saline before HIFU ablation. HIFU sonication started at 6 min after administration of SonoVue or saline in Groups A and C, whereas it started at 10 min in Groups B and D. On day 1 after HIFU, magnetic resonance imaging was performed. Patients were followed up via phone or clinic visit during the first week after HIFU. RESULTS: No significant difference was observed in terms of age, fibroid location, diameter of fibroids, signal intensity on T2-weighted imaging, or tumour volume among the four groups (p > 0.05). The use of SonoVue significantly shortened the treatment time and sonication time. The sonication start time of 6 min, relative to 10 min, had significant effects on the treatment time and sonication time. The use of intravenous SonoVue followed by HIFU ablation 6 min later significantly increased the rate of significant grey-scale changes (55.9%) and the non-perfused volume ratio (94.2% ± 10.6%). No significant differences were observed in the incidence of intra-procedure and post-HIFU adverse effects among the four groups (p > 0.05). CONCLUSIONS: SonoVue could be safely used to enhance the ablation effects of HIFU treatment of uterine fibroids.


Asunto(s)
Medios de Contraste/administración & dosificación , Ultrasonido Enfocado de Alta Intensidad de Ablación , Leiomioma/cirugía , Microburbujas , Fosfolípidos/administración & dosificación , Hexafluoruro de Azufre/administración & dosificación , Neoplasias Uterinas/cirugía , Adulto , Femenino , Humanos , Leiomioma/diagnóstico por imagen , Leiomioma/patología , Imagen por Resonancia Magnética , Persona de Mediana Edad , Resultado del Tratamiento , Carga Tumoral , Neoplasias Uterinas/diagnóstico por imagen , Neoplasias Uterinas/patología
7.
Oncotarget ; 15: 614-633, 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39288289

RESUMEN

Restoration of the p53 pathway has been a long-term goal in the field of cancer research to treat tumors with mutated p53 and aggressive clinical behavior. p53 pathway restoration in p53-deficient cancers can be achieved by small molecules via p53-dependent or p53-independent processes. Hereafter p53-independent restoration of p53-pathway-signaling in p53-deficient/mutated tumors is referred to as 'restoration of the p53 pathway'. We compare activation of p53 target genes by novel compounds PG3 and PG3-Oc, that activate p53-target genes in a p53-independent manner, and four mutant p53-activating compounds while Nutlin-3a is used as negative control. PG3 and PG3-Oc upregulate p21, PUMA, and DR5 in five cancer cell lines with various p53 mutational statuses through ATF4 (Activating Transcriptional Factor 4) and integrated stress response (ISR) independent of p53. Mutant p53-targeting compounds induce expression of the 3 major downstream p53 target genes and ATF4 in a highly variable and cell-type-dependent manner. PG3 treatment activates ATF4 through ISR via kinase HRI (Heme-Regulated Inhibitor). ATF4 mediates upregulation of PUMA, p21, and NAG-1/GDF15 (Nonsteroidal anti-inflammatory drug-activated gene 1). We note that PUMA mediates apoptosis through activation of caspase-8 in HT29 cells and potentially caspase-10 in SW480 cells. We provide a novel mechanism engaged by PG3 to induce cell death via the HRI/ATF4/PUMA axis. Our results provide unique insights into the mechanism of action of PG3 as a novel cancer therapeutic targeting p53 pathway-like tumor suppression.


Asunto(s)
Apoptosis , Transducción de Señal , Proteína p53 Supresora de Tumor , Humanos , Proteína p53 Supresora de Tumor/metabolismo , Proteína p53 Supresora de Tumor/genética , Apoptosis/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Línea Celular Tumoral , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Neoplasias/genética , Neoplasias/patología , Factor de Transcripción Activador 4/metabolismo , Factor de Transcripción Activador 4/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Antineoplásicos/farmacología , Proteínas Reguladoras de la Apoptosis/metabolismo , Proteínas Reguladoras de la Apoptosis/genética , Mutación , Proteínas Proto-Oncogénicas
8.
Front Psychiatry ; 15: 1404059, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39077625

RESUMEN

Introduction: Schizophrenia is a severe and enduring psychiatric disorder, characterized by substantial challenges in achieving symptomatic remission. Up to now, there have been limited studies examining the association between remission status and social support in patients with schizophrenia during COVID-19. This study aimed to investigate the remission status of community-dwelling schizophrenia patients during the pandemic and explore whether symptomatic remission is significantly associated with social support in a cross-sectional study. Methods: 727 schizophrenia patients were recruited using a cluster random sampling method in the local community. Face-to-face interviews were used to gather data on participants' clinical characteristics, sociodemographic, social support, and symptomatic remission criteria. Logistic regression models were deployed to identify potential relationships between symptomatic remission and social support. Results: Among the 727 patients in our study, a substantial proportion of 522 (71.80%) achieved symptomatic remission, while 205 (28.2%) did not. Remarkably, those who achieved symptomatic remission exhibited a higher level of social support (28.32 ± 6.82) compared to those who did not. The proportion of patients achieving symptomatic remission in the low (19.4%), medium (46.2%), and high (34.3%) social support groups was 56.7%, 66.1%, and 88.0%, respectively. Moreover, the crude odds ratio for the association between social support and symptomatic remission was 3.20 (95% CI: 2.45-4.18). After controlling for all confounding factors, the adjusted odds ratio remained significant at 3.02 (95% CI: 2.30-3.97). Discussion: This consistent association underscores the critical role of social support in influencing symptomatic remission among community-dwelling schizophrenia patients, especially during the COVID-19 pandemic. Reinforcing the utilization of social support for fostering symptomatic remission among individuals with schizophrenia who reside in the community during such crises is recommended.

9.
J Neurosurg Spine ; 41(3): 316-324, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-38905714

RESUMEN

OBJECTIVE: There is still controversy about whether it is necessary to perform prophylactic neurosurgical decompression for severe scoliosis (SS) with syringomyelia (SM) to reduce the risk of neurological complications during subsequent spinal correction. This study aimed to explore the safety and effectiveness of using traction-assisted single-stage spinal correction as a treatment for patients who had SS with SM (SS-SM). METHODS: The patients who had SS-SM without previous neurosurgical intervention and who underwent traction-assisted single-stage posterior spinal correction at a single center were included, and the initial, posttraction, and postoperative clinical data were reviewed. Based on preoperative MRI, the included patients were divided into two categories: those with versus those without Chiari malformation type I (CM-I-related SM [CS] vs idiopathic SM [IS]), and those with a moderate syrinx (MS) versus those with a large syrinx (LS). Different groups' traction and operation contributions were calculated for comparisons (CS vs IS, MS vs LS). RESULTS: A total of 28 patients were included. The initial mean major scoliosis was 101.0° with a mean flexibility of 21.4%. After the operation, the mean total correction rate for scoliosis was 63.9%. The mean traction and operation contributions were 61.5% and 38.5%, respectively. Most of the patients (75%) underwent spinal corrections without 3-column osteotomies, and only 1 patient reported postoperative regional numbness without motor deficits. No differences were found in the mean total correction rates, traction, and operation contributions when comparing CS versus IS and MS versus LS with the comparable initial clinical data (p > 0.05). More than 50% of the total corrections were achieved by preoperative traction in all groups. CONCLUSIONS: Traction-assisted single-stage spinal correction can safely and effectively correct SS-SM without prophylactic neurosurgical decompression under strict patient selection. Additionally, traction can achieve more than half of the final spinal correction, even for patients with varying sizes of SMs.


Asunto(s)
Descompresión Quirúrgica , Escoliosis , Siringomielia , Tracción , Humanos , Escoliosis/cirugía , Siringomielia/cirugía , Femenino , Masculino , Tracción/métodos , Adolescente , Descompresión Quirúrgica/métodos , Resultado del Tratamiento , Adulto , Adulto Joven , Malformación de Arnold-Chiari/cirugía , Malformación de Arnold-Chiari/complicaciones , Niño , Fusión Vertebral/métodos , Estudios Retrospectivos , Imagen por Resonancia Magnética , Procedimientos Neuroquirúrgicos/métodos
10.
J Affect Disord ; 353: 11-18, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38373515

RESUMEN

BACKGROUND: Poor mental health is prevalent among men who have sex with men (MSM), including MSM university students (MSMUS), causing a significant burden on their health and society. The study aimed to compare the difference in levels of depressive symptoms between Chinese MSMUS and non-MSMUS and test the mediating roles of social support and loneliness in the relationship between MSM status and depressive symptoms among male university students. METHODS: From June to October 2018, a total of 305 MSMUS and 2447 non-MSMUS from two cities in Sichuan province (China) were investigated using questionnaires. RESULTS: The proportion of depression in the MSMUS and non-MSMUS groups was 54.1 % and 36.4 %, respectively. MSM status, social support, and loneliness were all significantly associated with depressive symptoms among Chinese university students. Structural equation modelling showed that the association between MSM status and depressive symptoms was partially mediated by three indirect paths, including 1) via social support (mediated proportion = 19.4 %), 2) via loneliness (mediated proportion = 19.3 %), and 3) via social support and then loneliness (mediated proportion = 16.1 %). CONCLUSIONS: Depression was prevalent among university students in China, especially MSMUS. The findings increased our understanding of the mediating roles of social support and loneliness in the link between MSM status and depressive symptoms among Chinese male university students, which have great implications for designing interventions to improve their mental health. LIMITATION: The cross-sectional study design limited causal inferences.


Asunto(s)
Soledad , Minorías Sexuales y de Género , Humanos , Masculino , Soledad/psicología , Homosexualidad Masculina/psicología , Estudios Transversales , Universidades , Depresión/epidemiología , Depresión/psicología , Apoyo Social , Encuestas y Cuestionarios , Estudiantes/psicología
11.
Front Psychiatry ; 15: 1355708, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38628263

RESUMEN

Introduction: Cognitive Impairment (CI) in the elderly, encompassing conditions ranging from Mild Cognitive Impairment (MCI) to dementia, represents a growing public health concern globally. This study aims to investigate the prevalence and correlates of CI among individuals aged 80 and above. Methods: The study conducts 13,027 elderly individual's door-to-door surveys, followed by the cross-tabulation of analysis data, logistic regression analysis, and health condition assessments to examine various determinants of CI. Results: The current study's key findings demonstrate sub-statical correlations between CI and various factors, including educational attainment, marital status, and gender. Pronounced differences are evident between urban and rural demographics. Furthermore, aspects of social engagement, notably communication proficiency and sensory capabilities, exhibit a strong association with CI. Logistic regression analysis highlights that residing in rural areas (Odds Ratio [OR] = 0.637) and being female (OR = 0.71) are linked to a decreased risk of CI. In contrast, behavioral and health-related variables present a complex picture. Specifically, aggressive behavior (Adjusted OR = 1.881) and symptoms of depression (Adjusted OR = 0.549) contrast with conditions such as asthma (OR= 2.857) and cerebral infarction (OR=1.348), which elevate the risk of CI. Intriguingly, hyperlipidemia (OR= 0.671) appears to confer a protective effect against CI. Conclusion: The study highlights the complexity of factors affecting CI in the elderly, advocating for a comprehensive approach to understanding and managing cognitive health.

12.
CNS Neurosci Ther ; 30(5): e14760, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38775183

RESUMEN

AIMS: This study aimed to unravel the dehydration status of patients with cerebral venous sinus thrombosis (CVST) to facilitate the understanding of dehydration in CVST. METHODS: This was a multicenter retrospective study and three populations were recruited, namely, patients with CVST, CVST mimics, and healthy subjects. Blood samples were obtained 1-2 days after admission to assess dehydration status. Stata 15.1 was performed for statistical analysis. RESULTS: A total of 208 patients were diagnosed with CVST, 237 with CVST mimics, and 200 healthy individuals were enrolled. The urine specific gravity (USG, 1.020 [1.014, 1.029] vs. 1.017 [1.011, 1.021]) was higher in patients with CVST than in those with mimics (all p < 0.001). The percentage of USG >1.03 was also higher in CVST (22.6%) than in its mimics (6.3%, p < 0.001). With the development of CVST, USG (acute vs. sub-acute vs. chronic, 1.022 [1.015, 1.033] vs. 1.021 [1.015, 1.031] vs. 1.019 [1.014, 1.025]) decreased. All dehydration-related markers could not differentiate CVST from its mimics and healthy populations, and they were not associated with CVST severity and prognosis (p > 0.05). CONCLUSION: High levels of USG, especially USG >1.013, were more common in patients with CVST. Dehydration-related indices could not characterize CVST and were not associated with CVST severity and prognosis.


Asunto(s)
Deshidratación , Trombosis de los Senos Intracraneales , Humanos , Trombosis de los Senos Intracraneales/complicaciones , Trombosis de los Senos Intracraneales/sangre , Masculino , Femenino , Deshidratación/diagnóstico , Deshidratación/complicaciones , Adulto , Estudios Retrospectivos , Persona de Mediana Edad , Adulto Joven , Anciano
13.
Sci Data ; 11(1): 304, 2024 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-38503792

RESUMEN

Massive increases in the risks of depressive disorders and the ensuing suicide have become the overarching menace for children/adolescents. Despite global consensus to instigate psychological healthcare policy for these children/adolescents, their effects remain largely unclear neither from a small amount of official data nor from small-scale scientific studies. More importantly, in underprivileged children/adolescents in lower-middle-economic-status countries/areas, the data collection may not be as equally accessible as in developed countries/areas, thus resulting in underrepresented observations. To address these challenges, we released a large-scale and multi-center cohort dataset (n = 249,772) showing the effects of primary psychological healthcare on decreasing depression and suicidal ideation in these children/adolescents who were underrepresented in previous studies or current healthcare systems, including unattended children/adolescents, orphans, children/adolescents in especially difficult circumstances, and "left-behind" and "single-parenting" children/adolescents. We provided all individual data recording the depressive symptoms and suicide ideation that had been collected at baseline (Oct 2022) and half-year follow-up (May 2023) from practicing this psychological healthcare system.


Asunto(s)
Depresión , Ideación Suicida , Adolescente , Niño , Humanos , Depresión/psicología , Depresión/terapia , Factores Socioeconómicos , Estudios Multicéntricos como Asunto
14.
J Clin Invest ; 134(14)2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39007268

RESUMEN

Apoptosis is a form of programmed cell death that is mediated by intrinsic and extrinsic pathways. Dysregulation of and resistance to cell death are hallmarks of cancer. For over three decades, the development of therapies to promote treatment of cancer by inducing various cell death modalities, including apoptosis, has been a main goal of clinical oncology. Apoptosis pathways also interact with other signaling mechanisms, such as the p53 signaling pathway and the integrated stress response (ISR) pathway. In addition to agents directly targeting the intrinsic and extrinsic pathway components, anticancer drugs that target the p53 and ISR signaling pathways are actively being developed. In this Review, we discuss selected and promising anticancer therapies in various stages of development, including drug targets, mechanisms, and resistance to related treatments, focusing especially on B cell lymphoma 2 (BCL-2) inhibitors, TRAIL analogues, DR5 antibodies, and strategies that target p53, mutant p53, and the ISR.


Asunto(s)
Apoptosis , Neoplasias , Transducción de Señal , Proteína p53 Supresora de Tumor , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Neoplasias/metabolismo , Neoplasias/genética , Apoptosis/efectos de los fármacos , Proteína p53 Supresora de Tumor/metabolismo , Proteína p53 Supresora de Tumor/genética , Transducción de Señal/efectos de los fármacos , Animales , Antineoplásicos/uso terapéutico , Antineoplásicos/farmacología , Proteínas Proto-Oncogénicas c-bcl-2/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/genética
15.
Front Mol Biosci ; 10: 1148389, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37602328

RESUMEN

p53 is a transcription factor that regulates the expression of genes involved in tumor suppression. p53 mutations mediate tumorigenesis and occur in approximately 50% of human cancers. p53 regulates hundreds of target genes that induce various cell fates including apoptosis, cell cycle arrest, and DNA damage repair. p53 also plays an important role in anti-tumor immunity by regulating TRAIL, DR5, TLRs, Fas, PKR, ULBP1/2, and CCL2; T-cell inhibitory ligand PD-L1; pro-inflammatory cytokines; immune cell activation state; and antigen presentation. Genetic alteration of p53 can contribute to immune evasion by influencing immune cell recruitment to the tumor, cytokine secretion in the TME, and inflammatory signaling pathways. In some contexts, p53 mutations increase neoantigen load which improves response to immune checkpoint inhibition. Therapeutic restoration of mutated p53 can restore anti-cancer immune cell infiltration and ameliorate pro-tumor signaling to induce tumor regression. Indeed, there is clinical evidence to suggest that restoring p53 can induce an anti-cancer immune response in immunologically cold tumors. Clinical trials investigating the combination of p53-restoring compounds or p53-based vaccines with immunotherapy have demonstrated anti-tumor immune activation and tumor regression with heterogeneity across cancer type. In this Review, we discuss the impact of wild-type and mutant p53 on the anti-tumor immune response, outline clinical progress as far as activating p53 to induce an immune response across a variety of cancer types, and highlight open questions limiting effective clinical translation.

16.
J Biol Chem ; 286(33): 29408-29416, 2011 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-21697087

RESUMEN

Human glioblastoma multiforme cells demonstrate varying levels of sensitivity to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. Endoplasmic reticulum (ER) stress has been shown to trigger cell death through apoptosis. We therefore pursued a strategy of integrating clinically relevant investigational agents that cooperate mechanistically through the regulation of ER stress and apoptosis pathways. Nelfinavir belongs to the protease inhibitor class of drugs currently used to treat patients with HIV and is in clinical trials as an anti-tumor agent. We found that Nelfinavir treatment led to ER stress-induced up-regulation of the DR5 receptor. This transactivation was mediated by the transcription factor CCAAT/enhancer binding protein homologous protein (CHOP). We also determined that ER stress-induced ATF4 up-regulation was responsible for modulation of CHOP. In contrast, DR4 receptor expression was unchanged by Nelfinavir treatment. Combining Nelfinavir with TRAIL led to a significantly enhanced level of apoptosis that was abrogated by siRNA silencing of DR5. We provide evidence that Nelfinavir-induced ER stress modulates DR5 expression in human glioblastoma multiforme cells and can enhance TRAIL efficacy. These studies provide a potential mechanistic rationale for the use of the Food and Drug Administration-approved agent Nelfinavir in combination with DR5 agonists to induce apoptosis in human malignancies.


Asunto(s)
Apoptosis/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Glioblastoma/tratamiento farmacológico , Glioblastoma/metabolismo , Inhibidores de la Proteasa del VIH/farmacología , Nelfinavir/farmacología , Proteínas de Neoplasias/metabolismo , Receptores del Ligando Inductor de Apoptosis Relacionado con TNF/biosíntesis , Ligando Inductor de Apoptosis Relacionado con TNF/farmacología , Factor de Transcripción CHOP/metabolismo , Factor de Transcripción Activador 4/genética , Factor de Transcripción Activador 4/metabolismo , Línea Celular Tumoral , Glioblastoma/genética , Humanos , Proteínas de Neoplasias/genética , Receptores del Ligando Inductor de Apoptosis Relacionado con TNF/genética , Factor de Transcripción CHOP/genética , Respuesta de Proteína Desplegada/efectos de los fármacos , Respuesta de Proteína Desplegada/genética
17.
Psychiatry Res ; 317: 114841, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36113253

RESUMEN

OBJECTIVES: This study aims to investigate medication adherence during the COVID-19 pandemic among community-dwelling schizophrenia patients, and to explore the role of social support in improving medication adherence in a rural community sample in China. METHODS: A cross-sectional sample of 800 patients was recruited using a cluster random sampling method in Yingshan County, Sichuan Province. Information on participant demographic characteristics, social support and medication adherence was collected through face-to-face interviews. The data analysis was performed using SAS9.4. Two binary logistic regression models were employed to identify the association between regular medication use and social support. RESULTS: The rate of regular medication adherence among community-dwelling patients with schizophrenia was 41.5%,which was lower than that indicated by recent research(Li et al., 2020) before COVID-19 in western rural China. The mean scores and standard deviation of the patient's objective support, subjective support, and support utilization were 4.94 ± 1.57, 17.03 ± 5.24, and 5.25 ± 2.75, respectively. The social support standard deviation was 27.22 ± 6.32. The crude odds ratio of objective support, subjective support, and support utilization were 0.790 (95%CI:0.713-0.876), 0.999 (95%CI:0.971-1.027), and 1.049 (95%CI:0.995-1.105) respectively. After adjusting for potential factors, the adjusted odds ratio of objective support, subjective support, and support utilization were 0.758 (95%CI:0.673-0.853), 1.030 (95%CI:0.994-1.068), and 1.043 (95%CI:0.985-1.105), respectively. CONCLUSIONS: During the COVID-19 pandemic, community-dwelling schizophrenia patients had a low rate of regular medication adherence. This was particularly true of those who were older adults, less educated and living in rural areas. The results of this study suggest that strengthening social support may effectively improve medication adherence for those patients.


Asunto(s)
COVID-19 , Esquizofrenia , Humanos , Anciano , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/epidemiología , Estudios Transversales , Vida Independiente , Pandemias , Cumplimiento de la Medicación
18.
Biomolecules ; 12(4)2022 04 06.
Artículo en Inglés | MEDLINE | ID: mdl-35454137

RESUMEN

TP53 is a tumor suppressor gene that encodes a sequence-specific DNA-binding transcription factor activated by stressful stimuli; it upregulates target genes involved in growth suppression, cell death, DNA repair, metabolism, among others. TP53 is the most frequently mutated gene in tumors, with mutations not only leading to loss-of-function (LOF), but also gain-of-function (GOF) that promotes tumor progression, and metastasis. The tumor-specific status of mutant p53 protein has suggested it is a promising target for cancer therapy. We summarize the current progress of targeting wild-type and mutant p53 for cancer therapy through biotherapeutic and biopharmaceutical methods for (1) boosting p53 activity in cancer, (2) p53-dependent and p53-independent strategies for targeting p53 pathway functional restoration in p53-mutated cancer, (3) targeting p53 in immunotherapy, and (4) combination therapies targeting p53, p53 checkpoints, or mutant p53 for cancer therapy.


Asunto(s)
Neoplasias , Proteína p53 Supresora de Tumor , Muerte Celular , Humanos , Proteínas Mutantes/metabolismo , Mutación , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo
19.
J Epidemiol ; 21(5): 376-84, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21747208

RESUMEN

BACKGROUND: We assessed the effects of smoking and smoking cessation on life expectancy and active life expectancy among persons aged 55 years or older in Beijing. METHODS: This study included 1593 men and 1664 women who participated in the Beijing Longitudinal Study of Aging, which commenced in 1992 and had 4 survey waves up to year 2000. An abridged life table was used to estimate life expectancy, in which age-specific mortality and age-specific disability rates were adjusted by using a discrete-time hazard model to control confounders. RESULTS: The mean ages (SD) for men and women were 70.1 (9.25) and 70.2 (8.72) years, respectively; mortality and disability rates during follow-up were 34.7% and 8.0%, respectively. In both sexes, never smokers had the highest life expectancy and active life expectancy across ages, as compared with current and former smokers. Current heavy smokers had a shorter life expectancy and a shorter active life expectancy than light smokers. Among former smokers, male long-term quitters had a longer life expectancy and longer active life expectancy than short-term quitters, but this was not the case in women. CONCLUSIONS: Older adults remain at higher risk of mortality and morbidity from smoking and can expect to live a longer and healthier life after smoking cessation.


Asunto(s)
Esperanza de Vida/tendencias , Cese del Hábito de Fumar/estadística & datos numéricos , Fumar/epidemiología , Anciano , China/epidemiología , Personas con Discapacidad/estadística & datos numéricos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Medición de Riesgo , Distribución por Sexo , Fumar/mortalidad
20.
Front Aging Neurosci ; 13: 741881, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34880744

RESUMEN

A growing body of evidence indicates that atherosclerosis is correlated with cerebral small vessel disease and contributes to cognitive decline. This study aimed to explore the characteristics and contributions of intracranial hemodynamics and carotid atherosclerosis to cognitive dysfunction in subjects with subcortical ischemic vascular dementia (SIVD). Notably, 44 patients with SIVD, 30 patients with Alzheimer's disease (AD), and 30 healthy controls (HCs) were recruited from our longitudinal MRI study for AD and SIVD (ChiCTR1900027943). The cerebral mean flow velocity (MFV) and pulsatility index (PI) of both anterior and posterior circulations, artery plaque, and lumen diameter in carotid arteries were investigated using transcranial Doppler and carotid ultrasound, respectively. Their correlations with cognitive function were analyzed in patients with dementia. Decreased MFV and increased PI were found in patients with SIVD and AD. Patients with SIVD showed lower MFV and higher PI in the bilateral posterior cerebral arteries compared to patients with AD. Increases in lumen diameter, number of arteries with plaque, and total carotid plaque score were found in patients with SIVD. The Mini-Mental State Examination score was positively correlated with the MFV and negatively correlated with the PI of most major cerebral arteries, while it was negatively correlated with the lumen diameter of the common carotid artery, number of arteries with plaque, and total carotid plaque score in patients with dementia. There were also correlations between these parameters of some arteries and memory and executive function. Our results provide additional evidence suggesting that the pathological changes in macrovascular structure and function are correlated with cognitive impairment in dementia patients with SIVD and to a lesser extent AD.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA