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1.
J Neurophysiol ; 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38748436

RESUMO

BACKGROUND AND OBJECTIVES: The flexion synergy and extension synergy are a representative consequence of a stroke and appear in the upper extremity and lower extremity. Since the ipsilesional corticospinal tract (CST) is the most influential neural pathway for both extremities in motor execution, damage by a stroke to this tract could lead to similar motor pathological features (e.g., abnormal synergies) in both extremities. However, less attention has been paid to the inter-limb correlations in the flexion synergy and extension synergy across different recovery phases of a stroke. METHODS: We used results of the Fugl-Meyer assessment (FMA) to characterize those correlations in a total of 512 participants with hemiparesis post stroke from the acute phase to 1 year. The FMA provides indirect indicators of the degrees of the flexion synergy and extension synergy post stroke. RESULTS: We found that generally, strong inter-limb correlations (r>0.65 with all p-values<0.0001) between the flexion synergy and extension synergy appeared in the acute-to-subacute phase (<90 days). But correlations of lower-extremity extension synergy with upper-extremity flexion synergy and extension synergy decreased (down to r=0.38) around 360 days after stroke (p<0.05). DISCUSSION: These results suggest that preferential use of alternative neural pathways after damage by a stroke to the CST enhances inter-limb correlations between the flexion synergy and extension but a recovery of the CST functional and the fragmentation (remodeling) of the alternative neural substrates in the chronic phase contribute to diversity in neural pathways in motor execution, eventually leading to reduced inter-limb correlations.

2.
J Neurophysiol ; 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38691520

RESUMO

Stroke-caused synergies may result from preferential use of the reticulospinal tract (RST) due to damage to the corticospinal tract. The RST branches multiple motoneuron pools across the arm together resulting in gross motor control or muscle synergies, and accordingly the controllability of individual muscles is reduced. It is not clear whether the muscles involuntarily activated by abnormal synergy vary with the muscles voluntarily activated when motor commands descend through the RST. Studies showed that abnormal synergies may originate from merging and re-weighting of synergies individuals without neurological deficit. This leads to a hypothesis that those abnormal synergies are still selectively excited depending on the context. In this study, we test this hypothesis, leveraging the Fugl-Meyer assessment (FMA) that could characterize the neuroanatomical architecture in individuals with a wide range of impairment. We examine the ability to perform an out-of-synergy movement with the flexion synergy caused by either shoulder or elbow loading. The results reveal that about 14% (8/57, 95%CI: [5.0%, 23.1%]) of the participants with severe impairment (total FM score <29) in the chronic phase (6 months after stroke) are able to keep the elbow extended during shoulder loading and keep the shoulder at neutral during elbow loading. Those participants undergo a different course of neural reorganization which enhanced abnormal synergies in comparison with individuals with mild impairment (p<0.05). These results evidence that separate routes and synergy modules to motoneuron pools across the arm might exist even if the motor command is mediated possibly via the RST.

3.
Medicina (Kaunas) ; 60(4)2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38674206

RESUMO

Long-term changes in caregiver burden should be clarified considering that extended post-stroke disability can increase caregiver stress. We assessed long-term changes in caregiver burden severity and its predictors. This study was a retrospective analysis of the Korean Stroke Cohort for Functioning and Rehabilitation. Patients with an acute first-ever stroke were enrolled from August 2012 to May 2015. Data were collected at 6 months and 6 years after stroke onset. The caregiver burden was measured with a subjective caregiver burden questionnaire based on the Korean version of the Caregiver Burden Inventory. The caregivers' characteristics and patients' clinical and functional status were also examined at each follow-up. A high caregiver burden, which suggests a risk of burnout, was reported by 37.9% and 51.7% of caregivers at 6 months and 6 years post-stroke, respectively. Both the caregiver burden total score and proportion of caregivers at risk of burnout did not decrease between 6 months and 6 years. The patients' disability (OR = 11.60; 95% CI 1.58-85.08; p = 0.016), caregivers' self-rated stress (OR = 0.03; 95% CI 0.00-0.47; p = 0.013), and caregivers' quality of life (OR = 0.76; 95% CI 0.59-0.99; p = 0.042) were burden predictors at 6 months. At 6 years, only the patients' disability (OR = 5.88; 95% CI 2.19-15.82; p < 0.001) and caregivers' psychosocial stress (OR = 1.26; 95% CI 1.10-1.44; p = 0.001) showed significance. Nearly half of the caregivers were at risk of burnout, which lasted for 6 years after stroke onset. The patients' disability and caregivers' stress were burden predictors in both subacute and chronic phases of stroke. The findings suggest that consistent interventions, such as emotional support or counseling on stress relief strategies for caregivers of stroke survivors, may reduce caregiver burden. Further research is needed to establish specific strategies appropriate for Korean caregivers to alleviate their burden in caring for stroke patients.


Assuntos
Sobrecarga do Cuidador , Cuidadores , Qualidade de Vida , Acidente Vascular Cerebral , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/psicologia , Acidente Vascular Cerebral/complicações , Estudos Retrospectivos , Cuidadores/psicologia , Cuidadores/estatística & dados numéricos , Idoso , Inquéritos e Questionários , República da Coreia , Qualidade de Vida/psicologia , Sobrecarga do Cuidador/psicologia , Sobreviventes/psicologia , Sobreviventes/estatística & dados numéricos , Adulto , Estresse Psicológico/psicologia , Estresse Psicológico/complicações , Estresse Psicológico/etiologia , Reabilitação do Acidente Vascular Cerebral/psicologia , Reabilitação do Acidente Vascular Cerebral/estatística & dados numéricos
4.
Healthcare (Basel) ; 12(7)2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38610177

RESUMO

Nurses play a key role in providing integrated supportive care to cancer patients for their various needs. Efforts should be made to identify the competencies required for nurses providing integrated supportive care to cancer survivors, evaluate the competence level with reliable and reasonable tools, and continuously improve them. In Phase 1, the items of the scale were developed through a literature review and by conducting a focus group interview. In Phase 2, the validity and reliability of the scale were analyzed. A total of 504 nurses participated. Data were analyzed using item analysis, exploratory factor analysis, confirmatory factor analysis, Pearson's correlation with other scales, internal consistency, and split-half reliability. The developed scale consisted of 22 items. These items were grouped into five subscales and labeled as professionalism enhancement, care coordination, comprehensive nursing needs assessment, providing tailored information and education, and recurrence surveillance and secondary cancer prevention. Confirmatory factor analysis supported good convergent and discriminant validities. The criterion validity was verified. The internal consistency of the scale measured by Cronbach's α was 0.91. The developed scale is expected to be used as an instrument to identify cancer survivor integrated supportive care competencies of nurses in practice.

5.
Artigo em Inglês | MEDLINE | ID: mdl-38683717

RESUMO

Robot-assisted motor training is applied for neurorehabilitation in stroke patients, using motor imagery (MI) as a representative paradigm of brain-computer interfaces to offer real-life assistance to individuals facing movement challenges. However, the effectiveness of training with MI may vary depending on the location of the stroke lesion, which should be considered. This paper introduces a multi-task electroencephalogram-based heterogeneous ensemble learning (MEEG-HEL) specifically designed for cross-subject training. In the proposed framework, common spatial patterns were used for feature extraction, and the features according to stroke lesions are shared and selected through sequential forward floating selection. The heterogeneous ensembles were used as classifiers. Nine patients with chronic ischemic stroke participated, engaging in MI and motor execution (ME) paradigms involving finger tapping. The classification criteria for the multi-task were established in two ways, taking into account the characteristics of stroke patients. In the cross-subject session, the first involved a direction recognition task for two-handed classification, achieving a performance of 0.7419 (±0.0811) in MI and 0.7061 (±0.1270) in ME. The second task focused on motor assessment for lesion location, resulting in a performance of 0.7457 (±0.1317) in MI and 0.6791 (±0.1253) in ME. Comparing the specific-subject session, except for ME on the motor assessment task, performance on both tasks was significantly higher than the cross-subject session. Furthermore, classification performance was similar to or statistically higher in cross-subject sessions compared to baseline models. The proposed MEEG-HEL holds promise in improving the practicality of neurorehabilitation in clinical settings and facilitating the detection of lesions.


Assuntos
Algoritmos , Interfaces Cérebro-Computador , Eletroencefalografia , Aprendizado de Máquina , Reabilitação do Acidente Vascular Cerebral , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Eletroencefalografia/métodos , Reabilitação do Acidente Vascular Cerebral/métodos , Idoso , Imaginação/fisiologia , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/complicações , Robótica , Adulto , Desempenho Psicomotor , AVC Isquêmico/fisiopatologia , AVC Isquêmico/reabilitação , Imagens, Psicoterapia/métodos
6.
Cell Rep Med ; 5(3): 101461, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38460517

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal types of cancer, and novel treatment regimens are direly needed. Epigenetic regulation contributes to the development of various cancer types, but its role in the development of and potential as a therapeutic target for PDAC remains underexplored. Here, we show that PRMT1 is highly expressed in murine and human pancreatic cancer and is essential for cancer cell proliferation and tumorigenesis. Deletion of PRMT1 delays pancreatic cancer development in a KRAS-dependent mouse model, and multi-omics analyses reveal that PRMT1 depletion leads to global changes in chromatin accessibility and transcription, resulting in reduced glycolysis and a decrease in tumorigenic capacity. Pharmacological inhibition of PRMT1 in combination with gemcitabine has a synergistic effect on pancreatic tumor growth in vitro and in vivo. Collectively, our findings implicate PRMT1 as a key regulator of pancreatic cancer development and a promising target for combination therapy.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Animais , Humanos , Camundongos , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/genética , Linhagem Celular Tumoral , Epigênese Genética , Gencitabina , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Proteína-Arginina N-Metiltransferases/genética , Proteína-Arginina N-Metiltransferases/metabolismo , Proteína-Arginina N-Metiltransferases/uso terapêutico , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo
7.
Phytopathology ; : PHYTO10230397KC, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38451552

RESUMO

Pine, an evergreen conifer, is widely distributed worldwide. It is economically, scientifically, and ecologically important. However, pine wilt disease (PWD) induced by the pine wood nematode (PWN) adversely affects pine trees. Many studies have been conducted on the PWN and its beetle vectors to prevent the spread of PWD. However, studies providing a comprehensive understanding of the pine tree transcriptome in response to PWN infection are lacking. Here, we performed temporal profiling of the pine tree transcriptome using PWD-infected red pine trees, Pinus densiflora, inoculated with the PWN by RNA sequencing. Our analysis revealed that defense-responsive genes involved in cell wall modification, jasmonic acid signaling, and phenylpropanoid-related processes were significantly enriched 2 weeks after PWD infection. Furthermore, some WRKY-type and MYB-type transcription factors were upregulated 2 weeks after PWD infection, suggesting that these transcription factors might be responsible for the genome-wide reprogramming of defense-responsive genes in the early PWD stage. Our comprehensive transcriptome analysis will assist in developing PWD-resistant pine trees and identifying genes to diagnose PWD at the early stage of infection, during which large-scale phenotypic changes are absent in PWD-infected pine trees.

8.
Cancer Sci ; 115(4): 1283-1295, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38348576

RESUMO

Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations in circulating tumor deoxyribonucleic acid (ctDNA) have been reported as representative noninvasive prognostic markers for pancreatic ductal adenocarcinoma (PDAC). Here, we aimed to evaluate single KRAS mutations as prognostic and predictive biomarkers, with an emphasis on potential therapeutic approaches to PDAC. A total of 128 patients were analyzed for multiple or single KRAS mutations (G12A, G12C, G12D, G12R, G12S, G12V, and G13D) in their tumors and plasma using droplet digital polymerase chain reaction (ddPCR). Overall, KRAS mutations were detected by multiplex ddPCR in 119 (93%) of tumor DNA and 68 (53.1%) of ctDNA, with a concordance rate of 80% between plasma ctDNA and tumor DNA in the metastatic stage, which was higher than the 44% in the resectable stage. Moreover, the prognostic prediction of both overall survival (OS) and progression-free survival (PFS) was more relevant using plasma ctDNA than tumor DNA. Further, we evaluated the selective tumor-suppressive efficacy of the KRAS G12C inhibitor sotorasib in a patient-derived organoid (PDO) from a KRAS G12C-mutated patient using a patient-derived xenograft (PDX) model. Sotorasib showed selective inhibition in vitro and in vivo with altered tumor microenvironment, including fibroblasts and macrophages. Collectively, screening for KRAS single mutations in plasma ctDNA and the use of preclinical models of PDO and PDX with genetic mutations would impact precision medicine in the context of PDAC.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Proteínas Proto-Oncogênicas p21(ras)/genética , Biomarcadores Tumorais/genética , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/diagnóstico , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/genética , DNA de Neoplasias/genética , Mutação , Microambiente Tumoral
9.
J Am Heart Assoc ; 13(4): e032377, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38348806

RESUMO

BACKGROUND: Information on the long-term prognosis in patients with isolated thalamic stroke is sparse. We report the functional outcomes of patients with thalamic stroke up to 24 months from the KOSCO (Korean Stroke Cohort for Functioning and Rehabilitation) study. METHODS AND RESULTS: Isolated thalamic stroke was defined as the presence of lesions solely in the thalamus, excluding cases with lesions in other brain parenchyma areas apart from the thalamus, as identified by brain magnetic resonance imaging or computed tomography scans. The Fugl-Meyer Assessment, the Functional Ambulatory Category, the Korean Mini-Mental State Examination, the American Speech-Language-Hearing Association National Outcome Measurement System Swallowing Scale, and the short version of the Korean Frenchay Aphasia Screening Test were used to assess physical impairment. The Functional Independence Measure and modified Rankin Scale were used to assess functional outcomes. All measurements were conducted up to 24 months poststroke. A total of 297 patients were included, consisting of 235 with ischemic and 62 with hemorrhagic stroke. Except for the Functional Ambulatory Category and Functional Independence Measure, all physical impairments showed significant improvement up to 3 months poststroke (P<0.001) and reached a plateau. The Functional Ambulatory Category and Functional Independence Measure scores continued to improve up to 12 months poststroke (P<0.05) and reached a plateau. At 7 days poststroke, 47.5% of patients had no disability (modified Rankin Scale score<2), whereas at 24 months poststroke, 76.4% of patients had no significant disability. CONCLUSIONS: Patients showed rapid recovery from physical impairment up to 3 months poststroke, with additional improvements in ambulatory function and independence observed up to 12 months poststroke. Additionally, relatively favorable long-term functional prognosis at 24 months after onset was demonstrated. These results could provide insights into the proper management regarding functional outcomes of patients with isolated thalamic stroke.


Assuntos
Acidente Vascular Cerebral Hemorrágico , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/terapia , Prognóstico , Imageamento por Ressonância Magnética , Recuperação de Função Fisiológica
10.
Mar Environ Res ; 196: 106376, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38316569

RESUMO

The northeastern East China Sea is a highly dynamic marine ecosystem influenced by seasonally varying water mass properties. However, despite being among the world's fastest-warming ocean, there has been limited investigation into the impacts of warming on protistan communities. We collected seawater from two stations (E42 and E46) with different natural protist communities and environmental attributes to investigate the acclimation of the two communities to artificially elevated temperatures (ambient T, +2, and +4 °C). Nutrient and Chl-a conditions reflected oceanographic differences, providing insights into protistan community dynamics. Notably, small-sized autotrophic protists prevailed in the phosphate-deficient E42 community, with mid-incubation heterotrophic conversions. Higher temperatures exacerbated the effects of the P deficiency on the E42 community. While the proportions of Bacillariophyta increased only in the nutrient-balanced E46 communities, those of mixotrophic dinoflagellates increased with elevated temperature, regardless of P deficiency, suggesting that mixotrophy likely aids adaptation in changing marine environments. In summary, the findings of this microcosm study illuminate the potential modulation of spring protistan communities in the northeastern East China Sea under anticipated future warming.


Assuntos
Diatomáceas , Dinoflagellida , Ecossistema , Água do Mar , Diatomáceas/fisiologia , China , Fitoplâncton/fisiologia
11.
Biomed Pharmacother ; 173: 116319, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38422654

RESUMO

BACKGROUND: Effects of Dictamnus dasycarpus Turcz. on allergic asthma and their underlying mechanisms remain unclarified. Thus, we investigated the effects of D. dasycarpus Turcz. water extract (DDW) on mucus hypersecretion in mice with ovalbumin (OVA)-induced asthma and human bronchial epithelial cells. METHODS: BALB/c mice were used to establish an OVA-induced allergic asthma model. Mice were grouped into the OVA sensitization/challenge, 100 and 300 mg/kg DDW treatment, and dexamethasone groups. In mice, cell counts in bronchoalveolar lavage fluid (BALF), serum and BALF analyses, and histopathological lung tissue analyses were performed. Furthermore, we confirmed the basic mechanism in interleukin (IL)-4/IL-13-treated human bronchial epithelial cells through western blotting. RESULTS: In OVA-induced asthma mice, DDW treatment reduced inflammatory cell number and airway hyperresponsiveness and ameliorated histological changes (immune cell infiltration, mucus secretion, and collagen deposition) in lung tissues and serum total immunoglobulin E levels. DDW treatment lowered BALF IL-4, IL-5, and IL-13 levels; reduced levels of inflammatory mediators, such as thymus- and activation-regulated chemokine, macrophage-derived chemokine, and interferon gamma-induced protein; decreased mucin 5AC (MUC5AC) production; decreased signal transducer and activator of transcription (STAT) 6 and STAT3 expression; and restored forkhead box protein A2 (FOXA2) expression. In IL-4/IL-13-treated human bronchial epithelial cells, DDW treatment inhibited MUC5AC production, suppressed STAT6 and STAT3 expression (related to mucus hypersecretion), and increased FOXA2 expression. CONCLUSIONS: DDW treatment modulates MUC5AC expression and mucus hypersecretion by downregulating STAT6 and STAT3 expression and upregulating FOXA2 expression. These findings provide a novel approach to manage mucus hypersecretion in asthma using DDW.


Assuntos
Asma , Dictamnus , Fator 3-beta Nuclear de Hepatócito , Fator de Transcrição STAT3 , Camundongos , Humanos , Animais , Interleucina-13/metabolismo , Interleucina-4/metabolismo , Ovalbumina , Modelos Animais de Doenças , Asma/induzido quimicamente , Asma/tratamento farmacológico , Pulmão , Inflamação/metabolismo , Muco/metabolismo , Líquido da Lavagem Broncoalveolar , Camundongos Endogâmicos BALB C , Citocinas/metabolismo , Fator de Transcrição STAT6/metabolismo
12.
Sci Rep ; 14(1): 4483, 2024 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-38396060

RESUMO

This study investigates whether simultaneous high-definition transcranial direct current stimulation (HD-tDCS) enhances the effects of robot-assisted gait training in stroke patients. Twenty-four participants were randomly allocated to either the robot-assisted gait training with real HD-tDCS group (real HD-tDCS group) or robot-assisted gait training with sham HD-tDCS group (sham HD-tDCS group). Over four weeks, both groups completed 10 sessions. The 10 Meter Walk Test, Timed Up and Go, Functional Ambulation Category, Functional Reach Test, Berg Balance Scale, Dynamic Gait Index, Fugl-Meyer Assessment, and Korean version of the Modified Barthel Index were conducted before, immediately after, and one month after the intervention. The real HD-tDCS group showed significant improvements in the 10 Meter Walk Test, Timed Up and Go, Functional Reach Test, and Berg Balance Scale immediately and one month after the intervention, compared with before the intervention. Significant improvements in the Dynamic Gait Index and Fugl-Meyer Assessment were also observed immediately after the intervention. The sham HD-tDCS group showed no significant improvements in any of the tests. Application of HD-tDCS during robot-assisted gait training has a positive effect on gait and physical function in chronic stroke patients, ensuring long-term training effects. Our results suggest the effectiveness of HD-tDCS as a complementary tool to enhance robotic gait rehabilitation therapy in chronic stroke patients.


Assuntos
Robótica , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Estimulação Transcraniana por Corrente Contínua , Humanos , Estimulação Transcraniana por Corrente Contínua/métodos , Robótica/métodos , Reabilitação do Acidente Vascular Cerebral/métodos , Acidente Vascular Cerebral/terapia , Marcha/fisiologia , Resultado do Tratamento
13.
medRxiv ; 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38370652

RESUMO

Objective: The flexion synergy and extension synergy are a representative consequence of a stroke and appear in the upper extremity and lower extremity. Since the ipsilesional corticospinal tract (CST) is the most influential neural pathway for both extremities in motor execution, damage by a stroke to this tract could lead to similar motor pathological features (e.g., abnormal synergies) in both extremities. However less attention has been paid to the inter-limb correlations in the flexion synergy and extension synergy across different recovery phases of a stroke. Methods: In this study, we used results of the Fugl-Meyer assessment (FMA) to characterize those correlations in a total of 512 participants with hemiparesis post stroke from the acute phase to 1 year. The FMA provides indirect indicators of the degrees of the flexion synergy and extension synergy post stroke. Results: We found that generally, strong inter-limb correlations (r>0.65 with all p-values<0.0001) between the flexion synergy and extension synergy appeared in the acute-to-subacute phase (<90 days). But correlations of lower-extremity extension synergy with upper-extremity flexion synergy and extension synergy decreased (down to r=0.38) around 360 days after stroke (p<0.05). Interpretation: These results suggest that the preferential use of alternative neural pathways after damage by a stroke to the CST enhances inter-limb correlations between the flexion synergy and extension, however a recovery of the CST or/and the functional fragmentation (remodeling) of the alternative neural substrates in the chronic phase contribute to diversity in neural pathways in motor execution, eventually leading to reduced inter-limb correlations.

14.
J Proteome Res ; 23(3): 905-915, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38293943

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis due to the absence of diagnostic markers and molecular targets. Here, we took an unconventional approach to identify new molecular targets for pancreatic cancer. We chose uncharacterized protein evidence level 1 without function annotation from extensive proteomic research on pancreatic cancer and focused on proline and serine-rich 2 (PROSER2), which ranked high in the cell membrane and cytoplasm. In our study using cell lines and patient-derived orthotopic xenograft cells, PROSER2 exhibited a higher expression in cells derived from primary tumors than in those from metastatic tissues. PROSER2 was localized in the cell membrane and cytosol by immunocytochemistry. PROSER2 overexpression significantly reduced the metastatic ability of cancer cells, whereas its suppression had the opposite effect. Proteomic analysis revealed that PROSER2 interacts with STK25 and PDCD10, and their binding was confirmed by immunoprecipitation and immunocytochemistry. STK25 knockdown enhanced metastasis by decreasing p-AMPK levels, whereas PROSER2-overexpressing cells increased the level of p-AMPK, indicating that PROSER2 suppresses invasion via the AMPK pathway by interacting with STK25. This is the first demonstration of the novel role of PROSER2 in antagonizing tumor progression via the STK25-AMPK pathway in PDAC. LC-MS/MS data are available at MassIVE (MSV000092953) and ProteomeXchange (PXD045646).


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Animais , Humanos , Proteínas Quinases Ativadas por AMP , Cromatografia Líquida , Proteômica , Proliferação de Células , Movimento Celular , Espectrometria de Massas em Tandem , Neoplasias Pancreáticas/patologia , Carcinoma Ductal Pancreático/genética , Modelos Animais de Doenças , Proteínas Serina-Treonina Quinases , Peptídeos e Proteínas de Sinalização Intracelular
15.
Am J Phys Med Rehabil ; 103(4): 325-332, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37903631

RESUMO

OBJECTIVE: This study aimed to demonstrate the incidence of altered level of consciousness after hemorrhagic stroke and identify factors associated with altered level of consciousness at 3 mos after stroke. DESIGN: This study used data from a prospective multicenter cohort study conducted in nine hospitals in Korea and included 1677 patients with first-ever hemorrhagic stroke. Patients were dichotomized into those with and without altered level of consciousness at 3 mos after stroke. Multivariate logistic regression analysis was performed to identify factors associated with subacute to chronic stage altered level of consciousness. RESULTS: Among patients with hemorrhagic stroke (age: 20-99 yrs, female 50.21%), the prevalence of altered level of consciousness at admission was 38.58% (25.4% [drowsy], 6.38% [stupor], and 6.8% [coma]) and 17.29% 3 mos after stroke. Multivariate logistic regression analysis revealed that independent factors associated with altered level of consciousness at 3 mos after stroke included late seizure (odds ratio [95% confidence interval], 5.93 [1.78-20.00]), stroke progression (3.84 [1.48-9.64]), craniectomy (2.19 [1.19-4.00]), history of complications (1.74 [1.18-2.55]), age at stroke onset (1.08 [1.07-1.10]), and initial Glasgow Coma Scale score category (0.36 [0.30-0.44]). CONCLUSIONS: The factors associated with altered level of consciousness at 3 mos after stroke should be considered when explaining long-term consciousness status and focused management of modifiable factors in acute care hospitals could help ameliorate altered level of consciousness and promote recovery after stroke.


Assuntos
Acidente Vascular Cerebral Hemorrágico , Acidente Vascular Cerebral , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Adulto Jovem , Estudos de Coortes , Estado de Consciência , Transtornos da Consciência/epidemiologia , Transtornos da Consciência/etiologia , Escala de Coma de Glasgow , Incidência , Estudos Prospectivos , República da Coreia/epidemiologia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/epidemiologia
16.
Genes (Basel) ; 14(11)2023 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-38003017

RESUMO

M. incognita, a root-knot nematode (RKN), infects the roots of several important food crops, including sweet potato (Ipomoea batatas Lam.), and severely reduces yields. However, the molecular mechanisms underlying infection remain unclear. Previously, we investigated differential responses to RKN invasion in susceptible and resistant sweet potato cultivars through RNA-seq-based transcriptome analysis. In this study, gene expression similarities and differences were examined in RKN-susceptible sweet potato cultivars during the compatible response to RKN infection. Three susceptible cultivars investigated in previous research were used: Dahomi (DHM), Shinhwangmi (SHM), and Yulmi (YM). Of the three cultivars, YM had the highest number of genes with altered expression in response to infection. YM was also the cultivar with the highest susceptibility to RKN. Comparisons among cultivars identified genes that were regulated in more than one cultivar upon infection. Pairwise comparisons revealed that YM and DHM shared the most regulated genes, whereas YM and SHM shared the lowest number of regulated genes. Five genes were up-regulated, and two were down-regulated, in all three cultivars. Among these, four genes were highly up-regulated in all cultivars: germin-like protein, anthranilate synthase α subunit, isocitrate lyase, and uncharacterized protein. Genes were also identified that were uniquely regulated in each cultivar in response to infection, suggesting that susceptible cultivars respond to infection through shared and cultivar-specific pathways. Our findings expand the understanding of the compatible response to RKN invasion in sweet potato roots and provide useful information for further research on RKN defense mechanisms.


Assuntos
Ipomoea batatas , Infecções por Nematoides , Tylenchoidea , Animais , Transcriptoma/genética , Ipomoea batatas/genética , Tylenchoidea/genética , Raízes de Plantas/genética , Raízes de Plantas/metabolismo , Doenças das Plantas/genética , Perfilação da Expressão Gênica
17.
Transplant Proc ; 55(9): 2143-2158, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37867003

RESUMO

BACKGROUND: Although liver transplantation (LT) is one of the definitive treatments for patients with end-stage liver failure, it inevitably results in ischemic reperfusion injury. It is known that prognosis is improved when temporary ischemic conditioning (IC) is applied to patients with ischemic reperfusion injury. The objective of this meta-analysis was to determine the short-term and long-term effects of IC on the clinical outcomes of LT recipients. METHODS: Randomized controlled studies on IC in patients with LTs were included. Patients were compared between an IC group and a sham group. Studies were retrieved from PubMed, Embase, and Cochrane Library. The risk of bias was evaluated using RoB 2.0. Mortality, graft function, and major complications were synthesized using RevMan 5.4.1. RESULTS: Among 316 papers, 17 articles (1196 patients) were included. There was an insignificant increase in short-term mortality (risk ratio [RR]: 3.00, 95% CI: 0.32-28.14, P = .34). However, long-term mortality was lower in the IC group than in the sham group, but not significantly (RR: 0.75; 95% CI: 0.47-1.20, P = .23). Short-term graft function (acute graft rejection and primary graft non-function) was not improved by IC. One-year graft loss tended to show better results in the IC group (RR: 0.53, 95% CI: 0.26-1.07, P = .08). CONCLUSION: Ischemic conditioning did not have a beneficial effect on LT. Although long-term outcomes appear to be better in the IC group than in the sham group, further randomized controlled trials are needed.


Assuntos
Transplante de Fígado , Traumatismo por Reperfusão , Humanos , Transplante de Fígado/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/prevenção & controle
18.
Medicine (Baltimore) ; 102(37): e34914, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37713857

RESUMO

Preoperative red blood cell (RBC) transfusion can induce immune modulation and alloimmunization; however, few studies have investigated the effect of preoperative transfusion and hemoglobin levels that need to be corrected before surgery, especially in critically ill patients such as those with end-stage liver disease who undergo liver transplantation (LT). This study aimed to investigate the effects of preoperative RBC transfusion on long-term mortality in LT recipients. A total of 249 patients who underwent LT at a single center between January 2012 and December 2021 were included in this study. The patients were divided into 2 groups: preoperative transfusion and preoperative non-transfusion. Since the baseline characteristics were significantly different between the 2 groups, we performed propensity score matching, including factors such as the Model for End-Stage Liver Disease score and intraoperative RBC transfusion, to exclude possible biases that could affect prognosis. We analyzed the 5-year mortality rate as the primary outcome. The preoperative transfusion group showed a 4.84-fold higher hazard ratio than that in the preoperative non-transfusion group. There were no differences in 30-day mortality, duration of intensive care unit stay, or graft rejection rate between the 2 groups. Preoperative transfusion could influence long-term mortality in LT, and clinicians should pay attention to RBC transfusion before LT unless the patient is hemodynamically unstable. A large-scale randomized controlled trial is needed to determine the possible mechanisms related to preoperative RBC transfusion, long-term mortality, and the level of anemia that should be corrected before surgery.


Assuntos
Doença Hepática Terminal , Transplante de Fígado , Humanos , Transfusão de Eritrócitos , Doença Hepática Terminal/cirurgia , Estudos Retrospectivos , Índice de Gravidade de Doença
19.
J Stroke Cerebrovasc Dis ; 32(10): 107302, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37703592

RESUMO

OBJECTIVES: This study aimed to analyze the factors affecting the long-term quality of life of patients with mild stroke and evaluate the differences according to age and sex. MATERIALS AND METHODS: The Korean Stroke Cohort for functioning and rehabilitation data was used, and patients with mild stroke with a National Institute of Health Stroke Scale score of < 5 were included. Quality of life after 6 months was analyzed using EuroQol-5 dimensions. Demographic and clinical characteristics were evaluated, and factors affecting the quality of life at 6 months were analyzed. RESULTS: Age, current drinking, marital status, length of stay, and modified Rankin Scale, Fugl-Meyer assessment, Functional Independence Measure, and Geriatric Depression Scale scores affected the quality of life at 6 months in patients with mild stroke. Fugl-Meyer assessment score was a predictor for those aged < 65 years, while the functional ambulatory category was a predictor for those aged ≥ 65 years. Predictors of quality of life, excluding alcohol consumption, were comparable between male and female. CONCLUSIONS: Among patients aged <65 years, individuals who consumed alcohol, and those who showed better motor function and fewer comorbidities had a higher quality of life. Among patients aged ≥65 years, quality of life was higher in males, younger age, married individuals, those with diabetes, and those with a better walking ability. Among male, individuals who consumed alcohol had a higher quality of life. Rehabilitation treatment should prioritize improving modifiable factors to enhance the quality of life in patients with mild stroke.


Assuntos
Qualidade de Vida , Acidente Vascular Cerebral , Humanos , Feminino , Masculino , Idoso , Lactente , Estudos Prospectivos , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/terapia , Pacientes , Etanol
20.
Am J Sports Med ; 51(12): 3243-3250, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37681499

RESUMO

BACKGROUND: The incidence of rotator cuff tears is rapidly increasing, and operative techniques for rotator cuff repair have been developed. However, the rates of postoperative retear remain high. PURPOSE/HYPOTHESIS: The purpose was to determine the effects of human dermal fibroblasts (HDFs) with hyaluronic acid (HA) on tendon-to-bone healing in a rabbit model of chronic rotator cuff tear injury. It was hypothesized that HA would enhance HDF proliferation and that a combination of HA and HDFs would produce a synergistic effect on the healing of repaired rotator cuff tendons of rabbits. STUDY DESIGN: Controlled laboratory study. METHODS: For in vitro study, HDFs were plated on a 24-well plate. After 1 day, 2 wells were designated as the test group and treated with 0.75% HA in phenol red-free Dulbecco's modified Eagle medium (DMEM). An other 2 wells served as control groups and were treated with the same volume of phenol red-free DMEM without HA. Each group was duplicated, resulting in a total of 4 wells, with 2 wells in each group for replication purposes. The cells were incubated for 24 hours, followed by 72-hour cultivation. Absorbance ratios at 96 and 24 hours were compared to evaluate cell proliferation. For the in vivo study, a total of 24 rabbits were randomly allocated to groups A, B, and C (n = 8 each). Supraspinatus tendons were detached bilaterally and left for 6 weeks to establish a chronic rotator tear model. Torn tendons were subsequently repaired using the following injections: group A, 0.5 × 106 HDFs with HA; group B, HA only; and group C, saline only. At 12 weeks after repair, biomechanical tests and histological evaluation were performed. RESULTS: In vitro study showed that HDF proliferation significantly increased with HA (HDFs with HA vs HDFs without HA; 3.96 ± 0.09 vs 2.53 ± 0.15; P < .01). In vivo, group A showed significantly higher load-to-failure values than the other groups (53.8 ± 6.9 N/kg for group A, 30.6 ± 6.4 N/kg for group B, and 24.3 ± 7.6 N/kg for group C; P < .001). Histological evaluation confirmed that group A showed higher collagen fiber density and better collagen fiber continuity, tendon-to-bone interface maturation, and nuclear shape than the other groups (all P < .05). CONCLUSION: This controlled laboratory study verified the potential of the combination of HDFs and HA in enhancing healing in a chronic rotator cuff tear rabbit model. CLINICAL RELEVANCE: A potential synergistic effect on rotator cuff tendon healing may be expected from a combination of HDFs and HA.


Assuntos
Lesões do Manguito Rotador , Animais , Humanos , Coelhos , Lesões do Manguito Rotador/cirurgia , Lesões do Manguito Rotador/patologia , Ácido Hialurônico/farmacologia , Ácido Hialurônico/uso terapêutico , Cicatrização , Modelos Animais de Doenças , Tendões/cirurgia , Ruptura/cirurgia , Fibroblastos , Colágeno/farmacologia , Fenóis/farmacologia , Fenômenos Biomecânicos
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