Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 12.939
Filtrar
Mais filtros











Intervalo de ano de publicação
1.
Stem Cell Res Ther ; 15(1): 146, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38764070

RESUMO

BACKGROUND: Based on previous in vivo studies and human trials, intrathecal cell delivery is a safe and relevant therapeutic tool for improving patient's quality of life with neurological conditions. We aimed to characterise the safety profile of intrathecally delivered Mesenchymal stem cells (MSCs). METHODS: Ovid MEDLINE, Embase, Scopus, Cochrane Library, KCI-Korean Journal Database, and Web of Science. Databases were searched from their inception until April 13, 2023. Randomised Controlled Trials (RCTs) that compared intrathecal delivery of MSCs to controls in adult populations were included. Adverse events (AEs) were pooled and meta-analysed using DerSimonian-Laird random effects models with a correction factor 0.5 added to studies with zero count cells. Pooled AEs were described using Risk ratio (RR) and 95% confidence intervals (95% CI). Then, a random-effects meta-regress model on study-level summary data was performed to explore the relationship between the occurrence of AEs and covariates thought to modify the overall effect estimate. Finally, publication bias was assessed. RESULTS: 303 records were reviewed, and nine RCTs met the inclusion criteria and were included in the quantitative synthesis (n = 540 patients). MSCs delivered intrathecally, as compared to controls, were associated with an increased probability of AEs of musculoskeletal and connective tissue disorders (categorised by Common Terminology Criteria for Adverse Events-CTCAE version 5.0) (RR: 1.61, 95% CI 1.19-2.19, I2 = 0%). The random-effects meta-regress model suggested that fresh MSCs increased the probability of occurrence of AEs compared to cryopreserved MSCs (RR: 1.554; p-value = 0.048; 95% CI 1.004-2.404), and the multiple-dose, decreased the probability of AEs by 36% compared to single doses (RR: 0.644; p-value = 0.048; 95% CI 0.416-0.996); however, univariate random effects meta-regression models revealed a not significant association between the occurrence of AEs from MSCs intrathecal delivery and each covariate. CONCLUSIONS: Intrathecal delivery of MSCs was associated with a slight increase in AEs associated with musculoskeletal and connective tissue disorders, albeit without serious AEs. We conclude that intrathecal MSCs delivery is safe for patients with neurological conditions. However, further high-quality, large-scale RCTs are needed to confirm these findings.


Assuntos
Injeções Espinhais , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Doenças do Sistema Nervoso , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Transplante de Células-Tronco Mesenquimais/efeitos adversos , Transplante de Células-Tronco Mesenquimais/métodos , Doenças do Sistema Nervoso/terapia , Células-Tronco Mesenquimais/citologia
2.
Int J Mol Sci ; 25(9)2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38731911

RESUMO

In drug discovery, selecting targeted molecules is crucial as the target could directly affect drug efficacy and the treatment outcomes. As a member of the CCN family, CTGF (also known as CCN2) is an essential regulator in the progression of various diseases, including fibrosis, cancer, neurological disorders, and eye diseases. Understanding the regulatory mechanisms of CTGF in different diseases may contribute to the discovery of novel drug candidates. Summarizing the CTGF-targeting and -inhibitory drugs is also beneficial for the analysis of the efficacy, applications, and limitations of these drugs in different disease models. Therefore, we reviewed the CTGF structure, the regulatory mechanisms in various diseases, and drug development in order to provide more references for future drug discovery.


Assuntos
Fator de Crescimento do Tecido Conjuntivo , Descoberta de Drogas , Humanos , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Descoberta de Drogas/métodos , Animais , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Oftalmopatias/tratamento farmacológico , Oftalmopatias/metabolismo , Fibrose , Doenças do Sistema Nervoso/tratamento farmacológico , Doenças do Sistema Nervoso/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos
3.
Int J Immunopathol Pharmacol ; 38: 3946320241250293, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38712748

RESUMO

BACKGROUND: Cell metabolism functions without a stop in normal and pathological cells. Different metabolic changes occur in the disease. Cell metabolism influences biochemical and metabolic processes, signaling pathways, and gene regulation. Knowledge regarding disease metabolism is limited. OBJECTIVE: The review examines the cell metabolism of glucose, nucleotides, and lipids during homeostatic and pathological conditions of neurotoxicity, neuroimmunological disease, Parkinson's disease, thymoma in myasthenia gravis, and colorectal cancer. METHODS: Data collection includes electronic databases, the National Center for Biotechnology Information, and Google Scholar, with several inclusion criteria: cell metabolism, glucose metabolism, nucleotide metabolism, and lipid metabolism in health and disease patients suffering from neurotoxicity, neuroinflammation, Parkinson's disease, thymoma in myasthenia gravis. The initial number of collected and analyzed papers is 250. The final analysis included 150 studies out of 94 selected papers. After the selection process, 62.67% remains useful. RESULTS AND CONCLUSION: A literature search shows that signaling molecules are involved in metabolic changes in cells. Differences between cancer and neuroimmunological diseases are present in the result section. Our finding enables insight into novel therapeutic targets and the development of scientific approaches for cancer and neurological disease onset, outcome, progression, and treatment, highlighting the importance of metabolic dysregulation. Current understanding, emerging research technologies and potential therapeutic interventions in metabolic programming is disucussed and highlighted.


Assuntos
Glucose , Metabolismo dos Lipídeos , Neoplasias , Doenças do Sistema Nervoso , Nucleotídeos , Humanos , Neoplasias/metabolismo , Neoplasias/tratamento farmacológico , Doenças do Sistema Nervoso/metabolismo , Nucleotídeos/metabolismo , Glucose/metabolismo , Animais , Transdução de Sinais
4.
Pediatr Surg Int ; 40(1): 116, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38695977

RESUMO

PURPOSE: Existing guidelines provide weak recommendations on the surgical management of nutritional problems in children. The objective was to design a management pathway to address the best nutritional surgery (NS) procedure in a given patient. METHODS: Retrospective analysis of children treated at our department from January 2015 to December 2019. The sample was divided into two groups according to presence or absence of neurological impairment (NI). Patients with NI (Group 1) were classified in three subgroups based on presenting symptoms: A-Dysphagia without gastroesophageal reflux (GER); B-GER with or without dysphagia; C-Symptoms associated with a delayed gastric emptying. RESULTS: A total of 154 patients were included, 111 with NI. One-hundred-twenty-eight patients underwent only one procedure. Complications and mortality were superior in Group 1. In subgroup A, isolated gastrostomy was the first NS in all patients. In subgroup B most of patients were subjected to a Nissen fundoplication, while in 5 cases total esophagogastric dissociation (TEGD) was the first intervention. Considering the entire sample, 92.3% patients who underwent a TEGD did not require further procedures. CONCLUSION: NS encompasses various procedures depending on presenting symptoms and neurological status. A management flowchart for these patients is proposed.


Assuntos
Transtornos de Deglutição , Humanos , Estudos Retrospectivos , Feminino , Masculino , Criança , Pré-Escolar , Lactente , Transtornos de Deglutição/etiologia , Refluxo Gastroesofágico/cirurgia , Gastrostomia/métodos , Adolescente , Doenças do Sistema Nervoso , Fundoplicatura/métodos , Complicações Pós-Operatórias/epidemiologia
5.
Bol. latinoam. Caribe plantas med. aromát ; 23(3): 349-370, mayo 2024. ilus
Artigo em Inglês | LILACS | ID: biblio-1538077

RESUMO

Age-related neurological disorders (ANDs), including neurodegenerative diseases, are complex illnesses with an increasing risk with advancing years. The central nervous system's neuropathological conditions, including oxidative stress, neuroinflammation, and protein misfolding, are what define ANDs. Due to the rise in age-dependent prevalence, efforts have been made to combat ANDs. Vitis viniferahas a long history of usageto treat a variety of illness symptoms. Because multiple ligand sites may be targeted, Vitis viniferacomponents can be employed to treat ANDs. This is demonstrated by the link between the structure and action of these compounds. This review demonstrates that Vitis viniferaand its constituents, including flavonoids, phenolic compounds, stilbenoidsandaromatic acids, are effective at reducing the neurological symptoms and pathological conditions of ANDs. This is done by acting as an antioxidant and anti-inflammatory. The active Vitis vinifera ingredients have therapeutic effects on ANDs, as this review explains.


Las enfermedades neurológicas asociadas a la edad (AND, por su sigla en inglés) incluyendo las enfermedades neurodegenerativas, son enfermedades complejas con un riesgo creciente con la edad. Las condiciones neuropatológicas del sistema nervioso central, que incluyen el estrés oxidativo, la neuro inflamación, y el plegado erróneo de proteínas, son lo que define las AND. Debido al aumento en la prevalencia dependiente de la edad, se han hecho esfuerzos para combatir las AND. Vitis vinifera tiene una larga historia de uso para el tratamiento de síntomas. Puesto que puede hacer objetivo a muchos sitios ligando, los componentes de Vitis viniferase pueden utilizar para tratar AND. Esto se demuestra por el vínculo entre la estructura y la acción de estos compuestos. Esta revisión demuestra que la Vitis viniferay sus constituyentes, incluídos los flavonoides, componentes fenólicos, estilbenoides, y ácidos aromáticos, son efectivos para reducir los síntomas neurológicos y las condiciones patológicas de AND. Esto se produce por su acción como antioxidante y antiinflamatorio. Los ingredientes activos de Vitis vinifera tienen efectos terapéuticos en AND, y esta revisión lo explica.


Assuntos
Extratos Vegetais/uso terapêutico , Vitis/química , Doenças do Sistema Nervoso/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico
6.
Mymensingh Med J ; 33(2): 636-642, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38557550

RESUMO

Renal cell carcinoma (RCC) is derived from renal tubular epithelial cells and is among the 10 most common cancers worldwide. Incidence of renal cell carcinoma is 400,000 individuals worldwide per year. The age of diagnosis is approximately 60years, and twice as many men are diagnosed as women. African Americans have a slightly higher rate of RCC than do White peoples. The reasons for this are not clear. Inherited syndromes in family, long term dialysis, smoking individuals who had quit smoking >10 years prior had a lower risk when compared to those who had quit <10 years. 22.5 pack-year smokers had a more than 50.0% increased RCC risk compared to nonsmokers, high body mass index i.e. 5kg/m2 increase in body mass index (BMI) was found to be strongly associated with RCC. BMI >35kg/m2 is associated with higher incidence of Cancer raise blood pressure- Higher BMI and hypertension were independently shown to increase the long-term risk of RCC in men. A rise of blood pressure of 10mmHg is associated with 10-22 percent risk of RCC. Clear cell carcinoma is the most common variety of renal cell carcinoma as compared to other varieties of renal cell carcinomas (68.0-75.0%). It has also been found that CAIX is positive for all papillary renal cell carcinoma and negative for CK7, AMACR & TEF. We also found that CK7, EMA, CD117 and CAIX are most commonly positive for all chromophobe renal cell carcinoma. It has been found that clear cell carcinoma is the most common variety of renal cell carcinoma as compared to other varieties of renal cell carcinomas (68.0-75.0%). Again it has also been found that CAIX is positive for all papillary renal cell carcinoma and negative for CK7, AMACR and TEF. Here it has been found that chromophobe carcinoma is most commonly positive for CK7, EMA, CD117 and CAIX. In a patient coming with signs and symptoms of renal cell carcinoma can be confirmed with the help of histoimmunological markers and in that case one can plan for a proper planning of management.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Erros Inatos do Metabolismo Lipídico , Doenças do Sistema Nervoso , Racemases e Epimerases/deficiência , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Carcinoma de Células Renais/diagnóstico , Neoplasias Renais/diagnóstico , Biomarcadores Tumorais , Diálise Renal , Diagnóstico Diferencial
7.
Br J Community Nurs ; 29(4): 190-194, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38564446

RESUMO

Nearly 3 million people in the UK have a neurological condition; stroke, traumatic brain injury, Parkinson's disease, multiple sclerosis, brain tumour, motor neurone disease, among others - all affecting the person for the rest of their life. The NHS provides treatment at the onset of a condition but after that, there is a huge need for ongoing support. Research shows that those who are supported and know more about their condition are less likely to have to call on further in-hospital and GP care. There is enormous scope for improving the quality of life for those with neurological conditions. The right support-therapeutic and social-makes all the difference. The book, which this article is based on, shows how those with neurological conditions benefit from integrated ongoing support provided in the local community and self-help, and how lives can be improved. It explains good practice and encouraging methods in the support and treatment of those with life changing conditions.


Assuntos
Esclerose Múltipla , Doenças do Sistema Nervoso , Doença de Parkinson , Acidente Vascular Cerebral , Humanos , Qualidade de Vida , Doenças do Sistema Nervoso/terapia , Doença de Parkinson/terapia , Esclerose Múltipla/terapia
8.
Pediatr Transplant ; 28(3): e14728, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38600717

RESUMO

BACKGROUND: Although neurotoxicity is a major adverse event associated with busulfan, little information is available regarding the association between drug interactions and neurological symptoms during busulfan-based regimens. This study evaluated the association between prophylactic echinocandins and neurological complications in patients receiving busulfan-containing conditioning regimens for stem cell transplantation. METHODS: We retrospectively included consecutive patients who administered intravenous busulfan as a conditioning regimen at our facility between 2007 and 2022. Prophylactic echinocandin use was defined as the use of an echinocandin antifungal drug to prevent invasive fungal disease in SCT recipients. The primary outcome was the incidence of neurological complications within 7 days of busulfan initiation and was compared between the echinocandin group (patients received prophylactic echinocandin) and nonechinocandin group (patients received prophylactic antifungal drugs other than echinocandin and those without antifungal prophylaxis). RESULTS: Among the 59 patients included in this study, the incidence of neurological complications in the echinocandin (n = 26) and nonechinocandin groups (n = 33) was 30.8% and 63.6%, respectively. We observed a negative association between prophylactic echinocandin use and the development of neurological complications after adjusting for the propensity score for receiving prophylactic echinocandins (adjusted odds ratio 0.294, 95% confidence interval 0.090 to 0.959). We observed a lower incidence of neurological complications in the echinocandin group than in the nonechinocandin group. CONCLUSION: Our results suggested that the choice of antifungal prophylaxis is associated with busulfan neurotoxicity.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Doenças do Sistema Nervoso , Humanos , Bussulfano/efeitos adversos , Estudos Retrospectivos , Antifúngicos/uso terapêutico , Equinocandinas/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco , Doenças do Sistema Nervoso/etiologia , Condicionamento Pré-Transplante/efeitos adversos , Condicionamento Pré-Transplante/métodos , Doença Enxerto-Hospedeiro/etiologia
9.
Brain Nerve ; 76(4): 361-374, 2024 Apr.
Artigo em Japonês | MEDLINE | ID: mdl-38589281

RESUMO

Recent advances in genetic and antibody testing have limited pathological examination of peripheral nerve specimens. However, when examining peripheral neuropathological findings from a modern perspective, there is often an opportunity to comprehend previously unnoticed observations upon re-examining the same specimen. For example, electron microscopy studies have suggested that the components that distinguish between nodal regions and internodes play a pivotal role in the behavior of macrophages that initiate myelin phagocytosis in the demyelinating form of Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy (CIDP). Conversely, some patients previously diagnosed with CIDP were found to possess distinctive mechanisms initiated by autoantibodies against paranodal junction proteins such as neurofascin 155 leading to the emergence of the concept of autoimmune nodopathy. In vasculitis, the roles of neutrophils in antineutrophil cytoplasmic antibody-associated vasculitis, eosinophils in eosinophilic granulomatosis with polyangiitis, and complements in nonsystemic vasculitic neuropathy in tissue damage have also been demonstrated when viewed from a modern perspective. Furthermore, mechanisms attributable to predominant small-fiber loss in hereditary transthyretin amyloidosis have been clarified at an ultrastructural level.


Assuntos
Síndrome de Churg-Strauss , Granulomatose com Poliangiite , Doenças do Sistema Nervoso , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica , Humanos , Síndrome de Churg-Strauss/patologia , Granulomatose com Poliangiite/patologia , Axônios/patologia , Autoanticorpos
10.
Cell Death Dis ; 15(4): 269, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627369

RESUMO

Most of the patients affected by neuronopathic forms of Mucopolysaccharidosis type II (MPS II), a rare lysosomal storage disorder caused by defects in iduronate-2-sulfatase (IDS) activity, exhibit early neurological defects associated with white matter lesions and progressive behavioural abnormalities. While neuronal degeneration has been largely described in experimental models and human patients, more subtle neuronal pathogenic defects remain still underexplored. In this work, we discovered that the axon guidance receptor Deleted in Colorectal Cancer (Dcc) is significantly dysregulated in the brain of ids mutant zebrafish since embryonic stages. In addition, thanks to the establishment of neuronal-enriched primary cell cultures, we identified defective proteasomal degradation as one of the main pathways underlying Dcc upregulation in ids mutant conditions. Furthermore, ids mutant fish-derived primary neurons displayed higher levels of polyubiquitinated proteins and P62, suggesting a wider defect in protein degradation. Finally, we show that ids mutant larvae display an atypical response to anxiety-inducing stimuli, hence mimicking one of the characteristic features of MPS II patients. Our study provides an additional relevant frame to MPS II pathogenesis, supporting the concept that multiple developmental defects concur with early childhood behavioural abnormalities.


Assuntos
Iduronato Sulfatase , Mucopolissacaridose II , Doenças do Sistema Nervoso , Animais , Orientação de Axônios , Encéfalo/metabolismo , Iduronato Sulfatase/metabolismo , Mucopolissacaridose II/metabolismo , Doenças do Sistema Nervoso/patologia , Peixe-Zebra/metabolismo
11.
Cell Death Dis ; 15(4): 268, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627382

RESUMO

Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) represents the initial tumor suppressor gene identified to possess phosphatase activity, governing various cellular processes including cell cycle regulation, migration, metabolic pathways, autophagy, oxidative stress response, and cellular senescence. Current evidence suggests that PTEN is critical for stem cell maintenance, self-renewal, migration, lineage commitment, and differentiation. Based on the latest available evidence, we provide a comprehensive overview of the mechanisms by which PTEN regulates activities of different stem cell populations and influences neurological disorders, encompassing autism, stroke, spinal cord injury, traumatic brain injury, Alzheimer's disease and Parkinson's disease. This review aims to elucidate the therapeutic impacts and mechanisms of PTEN in relation to neurogenesis or the stem cell niche across a range of neurological disorders, offering a foundation for innovative therapeutic approaches aimed at tissue repair and regeneration in neurological disorders. This review unravels novel therapeutic strategies for tissue restoration and regeneration in neurological disorders based on the regulatory mechanisms of PTEN on neurogenesis and the stem cell niche.


Assuntos
Doenças do Sistema Nervoso , Doença de Parkinson , Humanos , Células-Tronco/metabolismo , Doenças do Sistema Nervoso/terapia , Doenças do Sistema Nervoso/metabolismo , Proliferação de Células , Doença de Parkinson/metabolismo , Diferenciação Celular , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo
12.
Sci Rep ; 14(1): 8750, 2024 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627418

RESUMO

This paper introduces a novel cable-driven robotic platform that enables six degrees-of-freedom (DoF) natural head-neck movements. Poor postural control of the head-neck can be a debilitating symptom of neurological disorders such as amyotrophic lateral sclerosis and cerebral palsy. Current treatments using static neck collars are inadequate, and there is a need to develop new devices to empower movements and facilitate physical rehabilitation of the head-neck. State-of-the-art neck exoskeletons using lower DoF mechanisms with rigid linkages are limited by their hard motion constraints imposed on head-neck movements. By contrast, the cable-driven robot presented in this paper does not constrain motion and enables wide-range, 6-DoF control of the head-neck. We present the mechatronic design, validation, and control implementations of this robot, as well as a human experiment to demonstrate a potential use case of this versatile robot for rehabilitation. Participants were engaged in a target reaching task while the robot applied both assistive and resistive moments on the head during the task. Our results show that neck muscle activation increased by 19% when moving the head against resistance and decreased by 28-43% when assisted by the robot. Overall, these results provide a scientific justification for further research in enabling movement and identifying personalized rehabilitation for motor training. Beyond rehabilitation, other applications such as applying force perturbations on the head to study sensory integration and applying traction to achieve pain relief may benefit from the innovation of this robotic platform which is capable of applying controlled 6-DoF forces/moments on the head.


Assuntos
Exoesqueleto Energizado , Doenças do Sistema Nervoso , Procedimentos Cirúrgicos Robóticos , Robótica , Humanos , Robótica/métodos , Movimento/fisiologia , Movimentos da Cabeça/fisiologia
13.
J Integr Neurosci ; 23(4): 86, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38682220

RESUMO

Due to the growth of the elderly population, age-related neurological disorders are an increasing problem. Aging begins very gradually and later leads to several neurological issues such as lower neurotransmitter levels, oxidative stress, neuronal inflammation, and continual neuronal loss. These changes might contribute to brain disorders such as Alzheimer's disease (AD), dementia or mild cognitive impairment, and epilepsy and glioma, and can also aggravate these disorders if they were previously present. Momordica charantia (bitter gourd), a member of the Cucurbitaceae family, is a good source of carbohydrates, proteins, vitamins, and minerals. It is used for diabetes and known for its hypoglycemic and antioxidant effects. In this review, we discuss the pharmaceutical effects of M. charantia on age-related neurological disorders. We searched several databases, including PubMed and Google Scholar, using MeSH terms. We searched articles published up until 2022 regardless of publication language. M. charantia is rich in luteolin, which increases acetylcholine in neurons by binding to enzymes in acetylcholine metabolism pathways, including butyrylcholinesterase and acetylcholinesterase. This binding inhibits the hyperphosphorylation of tau protein by restraining its kinase enzyme. Furthermore, this substance can lower serum cholesterol and has multi-target activity in AD and memory loss. M. charantia can also improve memory by decreasing tau protein and it also has potent antioxidant activity and anti-inflammatory effects. This review highlights that M. charantia has effects on many age-related neurological disorders, and can be a cost-effective supplement with minimal side effects.


Assuntos
Momordica charantia , Momordica charantia/química , Humanos , Animais , Envelhecimento/efeitos dos fármacos , Envelhecimento/fisiologia , Envelhecimento/metabolismo , Extratos Vegetais/farmacologia , Doenças do Sistema Nervoso/tratamento farmacológico , Doenças do Sistema Nervoso/metabolismo
14.
FEBS Lett ; 598(9): 959-977, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38644468

RESUMO

Reversible S-acylation plays a pivotal role in various biological processes, modulating protein functions such as subcellular localization, protein stability/activity, and protein-protein interactions. These modifications are mediated by acyltransferases and deacylases, among which the most abundant modification is S-palmitoylation. Growing evidence has shown that this rivalrous pair of modifications, occurring in a reversible cycle, is essential for various biological functions. Aberrations in this process have been associated with various diseases, including cancer, neurological disorders, and immune diseases. This underscores the importance of studying enzymes involved in acylation and deacylation to gain further insights into disease pathogenesis and provide novel strategies for disease treatment. In this Review, we summarize our current understanding of the structure and physiological function of deacylases, highlighting their pivotal roles in pathology. Our aim is to provide insights for further clinical applications.


Assuntos
Neoplasias , Humanos , Animais , Neoplasias/enzimologia , Neoplasias/metabolismo , Neoplasias/patologia , Neoplasias/genética , Aciltransferases/metabolismo , Aciltransferases/química , Doenças do Sistema Nervoso/enzimologia , Doenças do Sistema Nervoso/metabolismo , Acilação , Lipoilação , Processamento de Proteína Pós-Traducional , Doenças do Sistema Imunitário/enzimologia , Doenças do Sistema Imunitário/metabolismo
15.
Palliat Med ; 38(5): 582-592, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38679837

RESUMO

BACKGROUND: Variation in the provision of care and outcomes in the last months of life by cancer and non-cancer conditions is poorly understood. AIMS: (1) To describe patient conditions, symptom burden, practical problems, service use and dissatisfaction with end-of-life care for older adults based on the cause of death. (2) To explore factors related to these variables focussing on the causes of death. DESIGN: Secondary analysis of pooled data using cross-sectional mortality follow-back surveys from three studies: QUALYCARE; OPTCare Elderly; and International Access, Right, and Empowerment 1. SETTING/PARTICIPANTS: Data reported by bereaved relatives of people aged ⩾75 years who died of cancer, cardiovascular disease, respiratory disease, dementia or neurological disease. RESULTS: The pooled dataset contained 885 responses. Overall, service use and circumstances surrounding death differed significantly across causes of death. Bereaved relatives reported symptom severity from moderate to overwhelming in over 30% of cases for all causes of death. Across all causes of death, 28%-38% of bereaved relatives reported some level of dissatisfaction with care. Patients with cardiovascular disease and dementia experienced lower symptom burden and dissatisfaction than those with cancer. The absence of a reliable key health professional was consistently associated with higher symptom burden (p = 0.002), practical problems (p = 0.001) and dissatisfaction with care (p = 0.001). CONCLUSIONS: We showed different trajectories towards death depending on cause. Improving symptom burden and satisfaction in patients at the end-of-life is challenging, and the presence of a reliable key health professional may be helpful.


Assuntos
Doenças Cardiovasculares , Demência , Neoplasias , Assistência Terminal , Humanos , Masculino , Feminino , Idoso , Neoplasias/mortalidade , Neoplasias/psicologia , Demência/mortalidade , Demência/psicologia , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/mortalidade , Estudos Transversais , Doenças do Sistema Nervoso/mortalidade , Doenças Respiratórias/mortalidade , Causas de Morte , Satisfação do Paciente , Inquéritos e Questionários , Cuidados Paliativos , Efeitos Psicossociais da Doença , Carga de Sintomas
16.
Biochem Pharmacol ; 224: 116218, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38643906

RESUMO

Non-coding RNAs (ncRNAs) are an assorted collection of transcripts that are not translated into proteins. Since their discovery, ncRNAs have gained prominence as crucial regulators of various biological functions across diverse cell types and tissues, and their abnormal functioning has been implicated in disease. Notably, extensive research has focused on the relationship between microRNAs (miRNAs) and human cancers, although other types of ncRNAs, such as long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), are also emerging as significant contributors to human disease. In this review, we provide a comprehensive summary of our current knowledge regarding the roles of miRNAs, lncRNAs, and circRNAs in cancer and other major human diseases, particularly cancer, cardiovascular, neurological, and infectious diseases. Moreover, we discuss the potential utilization of ncRNAs as disease biomarkers and as targets for therapeutic interventions.


Assuntos
Neoplasias , RNA não Traduzido , Humanos , RNA não Traduzido/genética , RNA não Traduzido/metabolismo , Neoplasias/genética , Neoplasias/terapia , Neoplasias/metabolismo , Neoplasias/tratamento farmacológico , Animais , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/terapia , MicroRNAs/genética , MicroRNAs/metabolismo , Doenças do Sistema Nervoso/genética , Doenças do Sistema Nervoso/metabolismo , Doenças do Sistema Nervoso/terapia
18.
BMJ Open ; 14(4): e080628, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38653513

RESUMO

INTRODUCTION: There are great potential benefits of being able to conduct neuropsychological assessments remotely, especially for hard-to-reach or less mobile patient groups. Such tools need to be equivalent to standard tests done in the clinic and also easy to use in a variety of clinical populations. METHODS AND ANALYSIS: This study protocol describes a cross-sectional study aimed at validating the newly developed digitalized neuropsychological test battery Mindmore Remote in patients with neurological disorders and injuries. Diagnoses comprise traumatic brain injury, stroke, Parkinson's disease, multiple sclerosis, brain tumour and epilepsy. 50 patients in each patient group will be included. In addition, 50 healthy controls will be recruited. All participants will undergo both testing with Mindmore Remote at home and traditional neuropsychological assessment face-to-face in a randomised order. The primary outcome is the association between tests from the Mindmore Remote battery and their equivalent traditional neuropsychological tests. Further, bias between methods and differences between groups will also be investigated. ETHICS AND DISSEMINATION: The study protocol has been approved by the Swedish Ethical Review Authority (2022-06230-01) and adheres to the declaration of Helsinki. All participants will be given oral and written information about the study and sign informed consent forms before entering the study. All participants are informed that they can terminate their participation in the study at any given time, without giving any explanation, and participating in the study or not will not affect their care at the clinic. Neither authors nor personnel involved in the research project are affiliated with Mindmore AB. The results from the study will be published in peer-reviewed scientific journals and presented at national and international conferences on the topic. TRIAL REGISTRATION NUMBER: NCT05819008.


Assuntos
Testes Neuropsicológicos , Humanos , Estudos Transversais , Estudos de Casos e Controles , Doenças do Sistema Nervoso , Masculino , Projetos de Pesquisa , Suécia , Feminino
19.
Medicine (Baltimore) ; 103(14): e37721, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38579030

RESUMO

RATIONALE: White matter lesions (WMLs) are structural changes in the brain that manifest as demyelination in the central nervous system pathologically. Vasogenic WMLs are the most prevalent type, primarily associated with advanced age and cerebrovascular risk factors. Conversely, immunogenic WMLs, typified by multiple sclerosis (MS), are more frequently observed in younger patients. It is crucial to distinguish between these 2 etiologies. Furthermore, in cases where multiple individuals exhibit WMLs within 1 family, genetic testing may offer a significant diagnostic perspective. PATIENT CONCERNS: A 25-year-old male presented to the Department of Neurology with recurrent headaches. He was healthy previously and the neurological examination was negative. Brain magnetic resonance imaging (MRI) showed widespread white matter hyperintensity lesions surrounding the ventricles and subcortical regions on T2-weighted and T2 fluid-attenuated inversion recovery images, mimicking immunogenic disease-MS. DIAGNOSES: The patient was diagnosed with a patent foramen ovale, which could explain his headache syndrome. Genetic testing unveiled a previously unidentified missense mutation in the SERPINC1 gene in the patient and his father. The specific abnormal laboratory finding was a reduction in antithrombin III activity, and the decrease may serve as the underlying cause for the presence of multiple intracranial WMLs observed in both the patient and his father. INTERVENTIONS: The patient received percutaneous patent foramen ovale closure surgery and took antiplatelet drug recommended by cardiologists and was followed up for 1 month and 6 months after operation. OUTCOMES: While the lesions on MRI remain unchanging during follow-up, the patient reported a significant relief in headaches compared to the initial presentation. LESSONS: This case introduces a novel perspective on the etiology of cerebral WMLs, suggesting that hereditary antithrombin deficiency (ATD) could contribute to altered blood composition and may serve as an underlying cause in certain individuals with asymptomatic WMLs.


Assuntos
Deficiência de Antitrombina III , Forame Oval Patente , Esclerose Múltipla , Doenças do Sistema Nervoso , Doenças Vasculares , Substância Branca , Masculino , Humanos , Adulto , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Forame Oval Patente/patologia , Antitrombina III/genética , Deficiência de Antitrombina III/complicações , Deficiência de Antitrombina III/genética , Deficiência de Antitrombina III/patologia , Encéfalo/patologia , Imageamento por Ressonância Magnética/métodos , Doenças Vasculares/patologia , Doenças do Sistema Nervoso/patologia , Esclerose Múltipla/diagnóstico , Cefaleia , Mutação , Antitrombinas
20.
Mol Biol Rep ; 51(1): 563, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38647711

RESUMO

Adeno-associated virus (AAV) has emerged as a pivotal tool in neuroscience research, owing to its remarkable versatility and efficiency in delivering genetic material to diverse cell types within the nervous system. This mini review aims to underscore the advanced applications of AAV vectors in neuroscience and their profound potential to revolutionize our understanding of brain function and therapeutic interventions for neurological disorders. By providing a concise overview of the latest developments and strategies employing AAV vectors, this review illuminates the transformative role of AAV technology in unraveling the complexities of neural circuits and paving the way for innovative treatments. Through elucidating the multifaceted capabilities of AAV-mediated gene delivery, this review underscores its pivotal role as a cornerstone in contemporary neuroscience research, promising remarkable insights into the intricacies of brain biology and offering new avenues for therapeutic intervention.


Assuntos
Dependovirus , Técnicas de Transferência de Genes , Terapia Genética , Vetores Genéticos , Neurociências , Dependovirus/genética , Humanos , Vetores Genéticos/genética , Animais , Neurociências/métodos , Terapia Genética/métodos , Encéfalo/virologia , Encéfalo/metabolismo , Doenças do Sistema Nervoso/terapia , Doenças do Sistema Nervoso/virologia , Doenças do Sistema Nervoso/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA