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1.
J Plant Physiol ; 302: 154316, 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39098091

RESUMEN

ABA-insensitive 5 (ABI5) belongs to the basic leucine zipper class of transcription factors and is named for being the fifth identified Arabidopsis mutant unresponsive to ABA. To understand the influence of ABI5 in its active state on downstream gene expression and plant growth and development, we overexpressed the full-length ABI5 (A.t.MX-4) and the active forms of ABI5 with deleted transcriptional repression domains (A.t.MX-1, A.t.MX-2, and A.t.MX-3). Compared with the wild type, A.t.MX-1, A.t.MX-2, and A.t.MX-3 exhibited an increase in rosette leaf number and size, earlier flowering, increased thousand-seed weight, and significantly enhanced drought resistance. Thirty-five upregulated/downregulated proteins in the A.t.MX-1 were identified by proteomic analysis, and these proteins were involved in ABA biosynthesis and degradation, abiotic stress, fatty acid synthesis, and energy metabolism. These proteins participate in the regulation of plant drought resistance, flowering timing, and seed size at the levels of transcription and post-translational modification.

2.
Neuropsychol Rehabil ; : 1-30, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39078921

RESUMEN

Fatigue is common following paediatric acquired brain injury (ABI) and can negatively impact quality of life. Despite this, there is limited understanding of how clinicians currently assess and manage fatigue in rehabilitation. This study explored how Australian rehabilitation clinicians recognize, assess, and manage fatigue following paediatric ABI. Using a qualitative research design, semi-structured interviews were conducted with 11 clinicians who work with children (0-18 years) with ABI in rehabilitation. Interview transcripts were analysed using constructivist grounded theory methods. Two main themes and sub-themes were developed: (1) Reaching a shared understanding: Identifying and understanding fatigue; Unpacking fatigue with children and their families; and (2) Using the shared understanding: Clinicians working collaboratively to manage fatigue; Planning for and supporting children and their family through transitions; Anticipating and problem-solving speedbumps. Participants reflected on the importance of reaching a shared understanding of fatigue within each child's unique context, requiring the collaborative effort of the child, family, school, and interdisciplinary rehabilitation team, to problem-solve and manage fatigue together over time. These findings provide insights into the processes of assessing and managing fatigue from rehabilitation clinicians' perspectives and highlight the importance of a collaborative approach to support the individual needs of the child during their rehabilitation.

3.
Consort Psychiatr ; 5(1): 34-43, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39023113

RESUMEN

BACKGROUND: Psychotherapy for people with acquired brain injury (ABI) is considered to be an important component of a holistic neuropsychological rehabilitation approach. This helps in making sense of the loss of the sense of self they experience. Gender, premorbid personality, and socio-cultural discourses guide this process of understanding. Narrative formulation takes these considerations into account and, thus, can be used for formulating therapeutic plans. AIM: To present a case report which highlights the use of narrative case formulation to understand the psychological, social, and cultural factors forming the dominant discourse of a woman with ABI. METHODS: Ms. VA, a 43-year-old female, presented herself with a diagnosis of hypoxic ischemic encephalopathy with small chronic infarcts with gliosis in the bilateral cerebellar hemisphere, myoclonic seizures, mild cognitive impairment, depression, generalized dystonia, and bronchial asthma. Along with neuropsychological rehabilitation and cognitive retraining, 25 sessions of psychotherapy using narrative formulation were performed. RESULTS: Following the therapy, microgains such as a developing strong therapeutic relationship, accommodating vulnerability in her narrative, and finding moments of independence and assertion within the constraints of ABI were observed. Acceptance of her current predicament vis-à-vis her lost self and finding meaning in her new self were facilitated. CONCLUSION: There is paucity of research detailing psychotherapeutic management of ABI, especially in India. Psychotherapy, particularly using narrative formulation, can be helpful in understanding the intersections of gender role and expectations, premorbid personality and ABI, and aiding the post-ABI rehabilitation and adjustment. Future work in this area can explore the socio-cultural aspects that play an important role in the therapy process.

4.
NeuroRehabilitation ; 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39031393

RESUMEN

BACKGROUND: Acquired brain injuries (ABI) represent neurological disorders that can arise after traumatic and non-traumatic events. In addition to the physical, emotional and cognitive challenges that patients face, these injuries can bring changes in the life of the patient and his or her family. OBJECTIVE: This study aims to understand how the occurrence of an ABI condition can disrupt and reshape family functioning by examining certain dimensions such as role in the family, gender and age, which may have a major influence on family dynamics. METHODS: We enrolled 86 caregivers of patients with ABI. Two experienced psychologists examined family functioning with Olso's Family Adaptability and Cohesion Rating Scale (FACES IV). RESULTS: The correlation between groups by generics showed a significant difference only for flexibility (p = 0.05). Specifically, flexibility was greater in male caregivers, particularly in sons. Most of the constructs defining family functioning, such as communication, remained unchanged despite the ABI event. CONCLUSION: This study provides an in-depth understanding of how families face the challenges posed by the ABI and the role caregivers play within the system.

5.
Neuropsychol Rehabil ; : 1-27, 2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38870482

RESUMEN

Acquired Brain Injury (ABI) often results in significant challenges, yet it may also facilitate Post-Traumatic Growth (PTG). This review explores a critical question: "What are the main factors contributing to PTG following ABI, and what potential barriers to its development are perceived by ABI survivors?" Here we aim to systematically uncover these contributors and barriers to PTG through a meta-synthesis, involving a comprehensive review of previously published qualitative research on this topic. A literature search was conducted across PsycINFO, CINAHL, and MEDLINE up to December 2022 to identify studies for inclusion. From an initial pool of 1,946 records, eleven articles were selected for inclusion. Reflexive thematic analysis yielded three analytical themes including "Journey to Self-Rediscovery", "Strength in Connection" and "Overcoming Obstacles". Our findings also revealed facilitators and barriers across multiple levels of scale including personal (e.g., acceptance versus resignation), interpersonal (e.g., positive social ties versus difficulties making social connections), and systemic (e.g., new meaning and purpose versus financial constraints) scales. Our research extends existing knowledge in ABI rehabilitation, providing a more nuanced understanding of the dynamics influencing PTG with implications for clinicians seeking to promote wellbeing following brain injury.

6.
Front Plant Sci ; 15: 1395379, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38916028

RESUMEN

Introduction: The production of highly vigorous seeds with high longevity is an important lever to increase crop production efficiency, but its acquisition during seed maturation is strongly influenced by the growth environment. Methods: An association rule learning approach discovered MtABI4, a known longevity regulator, as a gene with transcript levels associated with the environmentally-induced change in longevity. To understand the environmental sensitivity of MtABI4 transcription, Yeast One-Hybrid identified a class I BASIC PENTACYSTEINE (MtBPC1) transcription factor as a putative upstream regulator. Its role in the regulation of MtABI4 was further characterized. Results and discussion: Overexpression of MtBPC1 led to a modulation of MtABI4 transcripts and its downstream targets. We show that MtBPC1 represses MtABI4 transcription at the early stage of seed development through binding in the CT-rich motif in its promoter region. To achieve this, MtBPC1 interacts with SWINGER, a sub-unit of the PRC2 complex, and Sin3-associated peptide 18, a sub-unit of the Sin3-like deacetylation complex. Consistent with this, developmental and heat stress-induced changes in MtABI4 transcript levels correlated with H3K27me3 and H3ac enrichment in the MtABI4 promoter. Our finding reveals the importance of the combination of histone methylation and histone de-acetylation to silence MtABI4 at the early stage of seed development and during heat stress.

7.
Plant Cell ; 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38924024

RESUMEN

Abscisic acid (ABA) signaling is crucial for plant responses to various abiotic stresses. The Arabidopsis (Arabidopsis thaliana) transcription factor ABA INSENSITIVE 5 (ABI5) is a central regulator of ABA signaling. ABI5 BINDING PROTEIN 1 (AFP1) interacts with ABI5 and facilitates its 26S-proteasome-mediated degradation, although the detailed mechanism has remained unclear. Here, we report that an ABA-responsive U-box E3 ubiquitin ligase, PLANT U-BOX 35 (PUB35), physically interacts with AFP1 and ABI5. PUB35 directly ubiquitinated ABI5 in a bacterially reconstituted ubiquitination system and promoted ABI5 protein degradation in vivo. ABI5 degradation was enhanced by AFP1 in response to ABA treatment. Phosphorylation of the T201 and T206 residues in ABI5 disrupted the ABI5-AFP1 interaction and affected the ABI5-PUB35 interaction and PUB35-mediated degradation of ABI5 in vivo. Genetic analysis of seed germination and seedling growth showed that pub35 mutants were hypersensitive to ABA as well as to salinity and osmotic stresses, whereas PUB35 overexpression lines were hyposensitive. Moreover, abi5 was epistatic to pub35, whereas the pub35-2 afp1-1 double mutant showed a similar ABA response to the two single mutants. Together, our results reveal a PUB35-AFP1 module involved in fine-tuning ABA signaling through ubiquitination and 26S-proteasome-mediated degradation of ABI5 during seed germination and seedling growth.

8.
Cancer Cell Int ; 24(1): 222, 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38937761

RESUMEN

Triple negative breast cancer (TNBC) is a type of cancer that lacks receptor expression and has complex molecular mechanisms. Recent evidence shows that the ubiquitin-protease system is closely related to TNBC. In this study, we obtain a key ubiquitination regulatory substrate-ABI2 protein by bioinformatics methods, which is also closely related to the survival and prognosis of TNBC. Further, through a series of experiments, we demonstrated that ABI2 expressed at a low level in TNBC tumors, and it has the ability to control cell cycle and inhibit TNBC cell migration, invasion and proliferation. Molecular mechanism studies proved E3 ligase CBLC could increase the ubiquitination degradation of ABI2 protein. Meanwhile, RNA-seq and IP experiments indicated that ABI2, acting as a crucial factor of tumor suppression, can significantly inhibit PI3K/Akt signaling pathway via the interaction with Rho GTPase RAC1. Finally, based on TNBC drug target ABI2, we screened and found that FDA-approved drug Colistimethate sodium(CS) has significant potential in suppressing the proliferation of TNBC cells and inducing cell apoptosis, making it a promising candidate for impeding the progression of TNBC.

9.
Plant Physiol Biochem ; 213: 108854, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38901228

RESUMEN

The transcription factors Related to ABI3/VP1 (RAV) are crucial for various plant processes and stress responses. Although the U's triangle Brassica species genomes have been released, the knowledge regarding the RAV family is still limited. In this study, we identified 123 putative RAV genes across the six U's triangle Brassica species (Brassica rapa, 14; Brassica oleracea, 14; Brassica nigra, 13; Brassica carinata, 27; Brassica juncea, 28; Brassica napus, 27). Phylogenetic analysis categorized them into three groups. The RAV genes exhibited diversity in both functional and structural aspects, particularly in gene structure and cis-acting elements within their promoters. The expression analysis revealed that BnaRAV genes in Group 1/2 exhibited diverse expression patterns across various tissues, while those in Group 3 did not show expression except for BnaRAV3L-2 and BnaRAV3L-6, which were exclusively expressed in seeds. Furthermore, the seed-specific expression of BnaA06. RAV3L (BnaRAV3L-2) was confirmed through promoter-GUS staining. Subcellular localization studies demonstrated that BnaA06.RAV3L is localized to the nucleus. The overexpression of BnaA06. RAV3L in Arabidopsis led to a remarkable inhibition of seed-specific traits such as seed width, seed length, seed area, and seed weight. This study provides insights into the functional evolution of the RAV gene family in U triangle Brassica species. It establishes a foundation for uncovering the molecular mechanisms underlying the negative role of RAV3L in seed development.


Asunto(s)
Brassica , Regulación de la Expresión Génica de las Plantas , Filogenia , Proteínas de Plantas , Semillas , Factores de Transcripción , Brassica/genética , Brassica/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Semillas/genética , Semillas/metabolismo , Semillas/crecimiento & desarrollo , Genoma de Planta , Arabidopsis/genética , Arabidopsis/metabolismo
10.
J Voice ; 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38897855

RESUMEN

OBJECTIVES: The purpose of this pilot study was to examine voice quality changes in individuals with early-stage Parkinson's disease (PD) utilizing the Acoustic Voice Quality Index (AVQI) and Acoustic Breathiness Index (ABI) over approximately a 1-year period. STUDY DESIGN: Follow-up study. METHODS: Baseline and follow-up data were gathered from the PDSTUlong speech corpus. The data for both time points included: speaker background information, sustained vowels, reading samples, and measures of PD severity (Hoehn and Yahr scores and Unified Parkinson's Disease Rating Scale III scores [UPDRS-III]). All speakers (N = 12) were native Finnish speakers. AVQIv03.01 and ABI analysis were completed in VOXplot v2.0.1. Changes in AVQI and ABI scores between baseline and follow-up were examined via causal analysis. Further, AVQI and ABI were analyzed in relation to measures of PD severity. RESULTS: Baseline mean AVQI score was 1.79 (range 0.14-4.83, SD=1.60), whereas follow-up mean AVQI score was 2.25 (range 0.55-4.53, SD=1.36). Baseline mean ABI score, in turn, was 2.92 (range 1-27 - 5.31, SD=1.57), whereas follow-up mean ABI score was 3.42 (range 1.40-5.40, SD=1.38). A significant difference was found between baseline and follow-up measures for both AVQI (Z = -2.002, P = 0.045) and ABI (Z = -2.197, P = 0.028). A significant difference in smoothed cepstral peak prominence (Z = -2.118, P = 0.034) and harmonics-to-noise ratio (Z = -1.961, P = 0.050) was also found between the two measurement periods. Change in AVQI and ABI were not correlated with the change in measures of PD severity. CONCLUSION: Over approximately 1-year, a statistical change was observed in AVQI and ABI scores, even in such a small dataset. The specific qualities of breathiness and hoarseness showed the most significant progression. Changes in voice quality were more prominent in ABI analysis.

12.
J Vasc Surg ; 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38866374

RESUMEN

BACKGROUND: Only a few small studies have shown the association between high ankle-brachial pressure index (ABI >1.4) and adverse cardiovascular (CV) events and mortality. Although there is abundant literature depicting the association between ABI and overall systemic atherosclerosis, it typically focuses on low ABI. Furthermore, historically, many studies focusing on peripheral artery disease have excluded high ABI participants. We aimed to study the mortality outcomes of persons with high ABI in the National Health and Nutrition Examination Survey (NHANES). METHODS: We obtained ABI from participants aged ≥40 years for survey years 1999 to 2004. We defined low a ABI as ≤0.9, normal ABI as 0.9 to 1.4, and high ABI as >1.4 or if the ankle pressures were >245 mm Hg. Demographics, various comorbidities, and laboratory test results were obtained at the time of the survey interview. Multivariable adjusted hazard ratios (HRs) along with 95% confidence intervals (CIs) were calculated for CV and all-cause mortality via Cox proportional hazards regression. Mortality was linked to all NHANES participants for follow-up through December 31, 2019, by the Centers for Disease Control and Prevention. RESULTS: We identified 7639 NHANES participants with available ABI. Of these, 6787 (89%) had a normal ABI, 646 (8%) had a low ABI, and 206 (3%) had elevated ABI. Of participants with high ABI, 50% were men, 15% were African Americans, 10% were current smokers, 56% had hypertension, 33% had diabetes, 15% had chronic kidney disease (CKD), and 18% had concomitant coronary artery disease (CAD). Diabetes (odds ratio [OR], 2.4; 95% CI, 1.7-3.2), CAD (OR, 1.6; 95% CI, 1.0-2.4), and CKD (OR, 1.5; 95% CI, 1.0-2.3) at baseline were associated with having a high ABI, respectively. A high ABI was associated independently with elevated CV (HR, 2.6; 95% CI, 2.1-3.1; P < .0001) and all-cause mortality (HR, 2.5; 95% CI, 2.2-2.8; P < .0001) after adjusting for covariates, including diabetes, CKD, CAD, current smoking, cancer, and hypertension. CONCLUSIONS: A high ABI is associated with an elevated CV and all-cause mortality, similar to patients with PAD. High ABI participants should receive the same attention and aggressive medical therapies as patients with PAD.

13.
Biochem Biophys Res Commun ; 723: 150190, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-38838447

RESUMEN

Soil salinity pose a significant challenge to global agriculture, threatening crop yields and food security. Understanding the salt tolerance mechanisms of plants is crucial for improving their survival under salt stress. AFP2, a negative regulator of ABA signaling, has been shown to play a crucial role in salt stress tolerance during seed germination. Mutations in AFP2 gene lead to increased sensitivity to salt stress. However, the underline mechanisms by which AFP2 regulates seed germination under salt stress remain elusive. In this study, we identified a protein interaction between AFP2 and SOS2, a Ser/Thr protein kinase known to play a critical role in salt stress response. Using a combination of genetic, biochemical, and physiological approaches, we investigated the role of the SOS2-AFP2 module in regulating seed germination under salt stress. Our findings reveal that SOS2 physically interacts with AFP2 and stabilizes it, leading to the degradation of the ABI5 protein, a negative transcription factor in seed germination under salt stress. This study sheds light on previously unknown connections within salt stress and ABA signaling, paving the way for novel strategies to enhance plant resilience against environmental challenges.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Germinación , Estrés Salino , Semillas , Arabidopsis/metabolismo , Arabidopsis/genética , Arabidopsis/crecimiento & desarrollo , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/metabolismo , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/genética , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Germinación/efectos de los fármacos , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Proteolisis/efectos de los fármacos , Tolerancia a la Sal/genética , Semillas/metabolismo , Semillas/efectos de los fármacos , Semillas/crecimiento & desarrollo , Semillas/genética , Transducción de Señal/efectos de los fármacos
14.
J Exp Bot ; 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38770693

RESUMEN

Plants combat dehydration stress through several adaptive measures including root architectural changes. Here we show that when exposed to varying levels of dehydration stress, primary root growth in Arabidopsis is modulated by regulating root meristem activity. ABA in concert with auxin signalling perceives the stress level and adapts primary root growth accordingly. ABI3, the ABA responsive transcription factor stands at the intersection of ABA and auxin signalling and fine tunes primary root growth in response to dehydration stress. Under low ABA or dehydration stress, induction of ABI3 expression promotes auxin signalling by decreasing expression of SHY2, a negative regulator of auxin response. This further enhances the expression of auxin transporter gene PIN1 and cell cycle gene CYCB1;1, resulting in an increase in primary root meristem size and root length. Higher levels of dehydration stress or ABA repress ABI3 expression and promote ABI5 expression. This elevates SHY2 expression, thereby impairing primary root meristem activity and retarding root growth. Notably, ABI5 can promote SHY2 expression only in the absence of ABI3. Such ABA concentration dependent expression of ABI3 therefore functions as a regulatory sensor of dehydration stress levels and orchestrates primary root growth by coordinating its downstream regulon.

15.
Trials ; 25(1): 340, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38778411

RESUMEN

BACKGROUND: Acquired brain injury (ABI) often leads to persisting somatic, cognitive, and social impairments. Cognitive impairments of processing speed, sustained attention, and working memory are frequently reported and may negatively affect activities of daily living and quality of life. Rehabilitation efforts aiming to retrain these cognitive functions have often consisted of computerized training programs. However, few studies have demonstrated effects that transfer beyond the trained tasks. There is a growing optimism regarding the potential usefulness of virtual reality (VR) in cognitive rehabilitation. The research literature is sparse, and existing studies are characterized by considerable methodological weaknesses. There is also a lack of knowledge about the acceptance and tolerability of VR as an intervention method for people with ABI. The present study aims to investigate whether playing a commercially available VR game is effective in training cognitive functions after ABI and to explore if the possible effects transfer into everyday functioning. METHODS: One hundred participants (18-65 years), with a verified ABI, impairments of processing speed/attention, and/or working memory, and a minimum of 12 months post injury will be recruited. Participants with severe aphasia, apraxia, visual neglect, epilepsy, and severe mental illness will be excluded. Participants will be randomized into two parallel groups: (1) an intervention group playing a commercial VR game taxing processing speed, working memory, and sustained attention; (2) an active control group receiving psychoeducation regarding compensatory strategies, and general cognitive training tasks such as crossword puzzles or sudoku. The intervention period is 5 weeks. The VR group will be asked to train at home for 30 min 5 days per week. Each participant will be assessed at baseline with neuropsychological tests and questionnaires, after the end of the intervention (5 weeks), and 16 weeks after baseline. After the end of the intervention period, focus group interviews will be conducted with 10 of the participants in the intervention group, in order to investigate acceptance and tolerability of VR as a training method. DISCUSSION: This study will contribute to improve understanding of how VR is tolerated and experienced by the ABI population. If proven effective, the study can contribute to new rehabilitation methods that persons with ABI can utilize in a home setting, after the post-acute rehabilitation has ended.


Asunto(s)
Atención , Lesiones Encefálicas , Cognición , Memoria a Corto Plazo , Humanos , Lesiones Encefálicas/rehabilitación , Lesiones Encefálicas/psicología , Persona de Mediana Edad , Adulto , Adolescente , Adulto Joven , Factores de Tiempo , Masculino , Anciano , Femenino , Resultado del Tratamiento , Juegos de Video , Ensayos Clínicos Controlados Aleatorios como Asunto , Actividades Cotidianas , Realidad Virtual , Pruebas Neuropsicológicas , Remediación Cognitiva/métodos , Terapia de Exposición Mediante Realidad Virtual/métodos , Recuperación de la Función , Transferencia de Experiencia en Psicología , Entrenamiento Cognitivo , Velocidad de Procesamiento
16.
Sci Prog ; 107(2): 368504241251649, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38780467

RESUMEN

BACKGROUND: Ankle-brachial index (ABI) measurement is a widely used diagnostic test for lower extremity artery disease. Previously, a larger body surface area (BSA) has been associated with lower blood pressure and lower 2-h post-load glucose concentrations in the oral glucose tolerance test. Our aim was to evaluate whether BSA has an impact on ABI and the prevalence of lower ABI values. METHODS: ABI measurements were performed on 972 subjects aged 45 to 70 years at high cardiovascular disease (CVD) risk. Subjects with previously diagnosed kidney disease, CVD, and diabetes were excluded. Their BSA was calculated by the Mosteller formula. Study subjects were divided into five BSA levels corresponding to 12.5th, 25th, 25th, 25th, and 12.5th percentiles of the total distribution. Effect modification by BSA in ABI between sexes was derived from a four-knot restricted cubic splines regression model. RESULTS: After adjustments for age, sex, pulse pressure, glucose regulation, waist circumference, alcohol intake, smoking status, leisure-time physical activity and medication, BSA level had a positive linear relationship with ABI (p for linearity <0.001). When BSA was less than 2.0 m2, there was no difference between the sexes, but when BSA was higher than 2.0 m2, men had higher ABI. CONCLUSION: BSA shows a positive linear relationship with ABI in CVD risk subjects without manifested CVD. The difference in ABI between men and women is modified by BSA and is appreciable when BSA is larger than 2.0 m2.


Asunto(s)
Índice Tobillo Braquial , Superficie Corporal , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Enfermedades Cardiovasculares/fisiopatología , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Enfermedad Arterial Periférica/fisiopatología , Enfermedad Arterial Periférica/diagnóstico , Enfermedad Arterial Periférica/epidemiología , Factores de Riesgo , Presión Sanguínea/fisiología
18.
Transl Oncol ; 45: 101992, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38743987

RESUMEN

CBLC (CBL proto-oncogene C) is an E3 ubiquitin protein ligase that plays a key role in cancers. However, the function and mechanism of CBLC in colorectal cancer (CRC) has not been fully elucidated. The aim of this study was to investigate the function of CBLC in CRC and its underlying molecular mechanism. High CBLC levels were certified in tumor tissues of CRC patients, and its expression was positively associated with TNM stage. Next, we explored the role of CBLC in CRC using gain or loss of function. For biological function analysis, CCK-8 cell proliferation, colony formation, flow cytometry, scratch, and transwell assays collectively suggested that CBLC overexpression promoted cell proliferation, cell cycle progression, migration and invasion. As observed, CBLC knockdown exhibited exactly opposite effects, resulting in impaired tumorigenicity in vitro. Xenograft studies displayed that CBLC overexpression accelerated tumor growth and promoted tumor metastasis to the lung, while the inhibitory effects of CBLC knockdown on tumorigenicity and metastasis ability of CRC cells was also confirmed. Furthermore, the molecular mechanism of CBLC in CRC was explored. CBLC induced the activation of ERK signaling pathway, further leading to its pro-tumor role. Notably, CBLC decreased ABI1 (Abelson interactor protein-1, a candidate tumor suppressor) protein levels through its ubiquitin ligase activity, while ABI1 upregulation abolished the effects of CBLC on the tumorigenesis of CRC. Taken together, these results demonstrate that CBLC acts as a tumor promoter in CRC through triggering the ubiquitination and degradation of ABI1 and activating the ERK signaling pathway. CBLC may be a potential novel target for CRC.

19.
J Surg Res ; 299: 290-297, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38788465

RESUMEN

INTRODUCTION: More than 1.2 million pulmonary artery catheters (PACs) are used in cardiac patients per annum within the United States. However, it is contraindicated in traditional 1.5 and 3T magnetic resonance imaging (MRI) scans. We aimed to test preclinical and clinical safety of using this imaging modality given the potential utility of needing it in the clinical setting. METHODS: We conducted two phantom experiments to ensure that the electromagnetic field power deposition associated with bare and jacketed PACs was safe and within the acceptable limit established by the Food and Drug Administration. The primary end points were the safety and feasibility of performing Point-of-Care (POC) MRI without imaging-related adverse events. We performed a preclinical computational electromagnetic simulation and evaluated these findings in nine patients with PACs on veno-arterial extracorporeal membrane oxygenation. RESULTS: The phantom experiments showed that the baseline point specific absorption rate through the head averaged 0.4 W/kg. In both the bare and jacketed catheters, the highest net specific absorption rates were at the neck entry point and tip but were negligible and unlikely to cause any heat-related tissue or catheter damage. In nine patients (median age 66, interquartile range 42-72 y) with veno-arterial extracorporeal membrane oxygenation due to cardiogenic shock and PACs placed for close hemodynamic monitoring, POC MRI was safe and feasible with good diagnostic imaging quality. CONCLUSIONS: Adult ECMO patients with PACs can safely undergo point-of-care low-field (64 mT) brain MRI within a reasonable timeframe in an intensive care unit setting to assess for acute brain injury that might otherwise be missed with conventional head computed tomography.


Asunto(s)
Encéfalo , Cateterismo de Swan-Ganz , Oxigenación por Membrana Extracorpórea , Imagen por Resonancia Magnética , Fantasmas de Imagen , Sistemas de Atención de Punto , Humanos , Masculino , Persona de Mediana Edad , Imagen por Resonancia Magnética/efectos adversos , Imagen por Resonancia Magnética/métodos , Femenino , Oxigenación por Membrana Extracorpórea/instrumentación , Oxigenación por Membrana Extracorpórea/efectos adversos , Oxigenación por Membrana Extracorpórea/métodos , Anciano , Adulto , Encéfalo/diagnóstico por imagen , Cateterismo de Swan-Ganz/instrumentación , Cateterismo de Swan-Ganz/efectos adversos , Estudios de Factibilidad
20.
J Transl Med ; 22(1): 514, 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38812032

RESUMEN

The aging process of the kidneys is accompanied with several structural diseases. Abnormal fiber formation disrupts the balance of kidney structure and function, causing to end-stage renal disease and subsequent renal failure. Despite this, the precise mechanism underlying renal damage in aging remains elusive. In this study, ABI3BP gene knockout mice were used to investigate the role of ABI3BP in renal aging induced by irradiation. The results revealed a significant increase in ABI3BP expression in HK2 cells and kidney tissue of aging mice, with ABI3BP gene knockout demonstrating a mitigating effect on radiation-induced cell aging. Furthermore, the study observed a marked decrease in Klotho levels and an increase in ferroptosis in renal tissue and HK2 cells following irradiation. Notably, ABI3BP gene knockout not only elevated Klotho expression but also reduced ferroptosis levels. A significant negative correlation between ABI3BP and Klotho was established. Further experiments demonstrated that Klotho knockdown alleviated the aging inhibition caused by ABI3BP downregulation. This study identifies the upregulation of ABI3BP in aged renal tubular epithelial cells, indicating a role in promoting ferroptosis and inducing renal aging by inhibiting Klotho expression.


Asunto(s)
Envejecimiento , Ferroptosis , Riñón , Proteínas Klotho , Ratones Noqueados , Animales , Humanos , Masculino , Ratones , Envejecimiento/metabolismo , Proteínas Portadoras/metabolismo , Proteínas Portadoras/genética , Línea Celular , Glucuronidasa/metabolismo , Riñón/metabolismo , Riñón/patología , Proteínas Klotho/metabolismo , Ratones Endogámicos C57BL
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