RESUMO
Epidemiological studies show that cardiovascular events related to platelet hyperactivity remain the leading causes of death among multiple sclerosis (MS) patients. Quantitative or structural changes of platelet cytoskeleton alter their morphology and function. Here, we demonstrated, for the first time, the structural changes in MS platelets that may be related to their hyperactivity. MS platelets were found to form large aggregates compared to control platelets. In contrast to the control, the images of overactivated, irregularly shaped MS platelets show changes in the cytoskeleton architecture, fragmented microtubule rings. Furthermore, MS platelets have long and numerous pseudopodia rich in actin filaments. We showed that MS platelets and megakaryocytes, overexpress ß1-tubulin and ß-actin mRNAs and proteins and have altered post-translational modification patterns. Moreover, we identified two previously undisclosed mutations in the gene encoding ß1-tubulin in MS. We propose that the demonstrated structural changes of platelet cytoskeleton enhance their ability to adhere, aggregate, and degranulate fueling the risk of adverse cardiovascular events in MS.
Assuntos
Plaquetas , Proteínas do Citoesqueleto , Citoesqueleto , Esclerose Múltipla , Tubulina (Proteína) , Humanos , Esclerose Múltipla/metabolismo , Esclerose Múltipla/patologia , Esclerose Múltipla/sangue , Plaquetas/metabolismo , Tubulina (Proteína)/metabolismo , Tubulina (Proteína)/genética , Feminino , Citoesqueleto/metabolismo , Proteínas do Citoesqueleto/genética , Proteínas do Citoesqueleto/metabolismo , Adulto , Masculino , Pessoa de Meia-Idade , Actinas/metabolismo , Actinas/genética , Megacariócitos/metabolismo , Megacariócitos/patologia , Processamento de Proteína Pós-Traducional , MutaçãoRESUMO
Multiple sclerosis (MS), traditionally perceived as a neurodegenerative disease, exhibits significant vascular alternations, including blood-brain barrier (BBB) disruption, which may predispose patients to increased cardiovascular risks. This vascular dysfunction is intricately linked with the infiltration of immune cells into the central nervous system (CNS), which plays a significant role in perpetuating neuroinflammation. Additionally, oxidative stress serves not only as a byproduct of inflammatory processes but also as an active contributor to neural damage. The synthesis of these multifaceted aspects highlights the importance of understanding their cumulative impact on MS progression. This review reveals that the triad of vascular damage, chronic inflammation, and oxidative imbalance may be considered interdependent processes that exacerbate each other, underscoring the need for holistic and multi-targeted therapeutic approaches in MS management. There is a necessity for reevaluating MS treatment strategies to encompass these overlapping pathologies, offering insights for future research and potential therapeutic interventions. Whole-body cryotherapy (WBCT) emerges as one of the potential avenues for holistic MS management approaches which may alleviate the triad of MS progression factors in multiple ways.
Assuntos
Esclerose Múltipla , Doenças Neurodegenerativas , Humanos , Esclerose Múltipla/terapia , Doenças Neuroinflamatórias , Crioterapia , Estresse OxidativoRESUMO
Despite the significant changes that unfold during the subacute phase of stroke, few studies have examined recovery abilities during this critical period. As neuroinflammation subsides and tissue degradation diminishes, the processes of neuroplasticity and angiogenesis intensify. An important factor in brain physiology and pathology, particularly neuroplasticity, is matrix metalloproteinase 9 (MMP-9). Its activity is modulated by tissue inhibitors of metalloproteinases (TIMPs), which impede substrate binding and activity by binding to its active sites. Notably, TIMP-1 specifically targets MMP-9 among other matrix metalloproteinases (MMPs). Our present study examines whether MMP-9 may play a beneficial role in psychological functions, particularly in alleviating depressive symptoms and enhancing specific cognitive domains, such as calculation. It appears that improvements in depressive symptoms during rehabilitation were notably linked with baseline MMP-9 plasma levels (r = -0.36, p = 0.025), and particularly so with the ratio of MMP-9 to TIMP-1, indicative of active MMP-9 (r = -0.42, p = 0.008). Furthermore, our findings support previous research demonstrating an inverse relationship between pre-rehabilitation MMP-9 serum levels and post-rehabilitation motor function. Crucially, our study emphasizes a positive correlation between cognition and motor function, highlighting the necessity of integrating both aspects into rehabilitation planning. These findings demonstrate the potential utility of MMP-9 as a prognostic biomarker for delineating recovery trajectories and guiding personalized treatment strategies for stroke patients during the subacute phase.
Assuntos
Metaloproteinase 9 da Matriz , Acidente Vascular Cerebral , Inibidor Tecidual de Metaloproteinase-1 , Metaloproteinase 9 da Matriz/sangue , Metaloproteinase 9 da Matriz/metabolismo , Humanos , Inibidor Tecidual de Metaloproteinase-1/sangue , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Masculino , Acidente Vascular Cerebral/metabolismo , Acidente Vascular Cerebral/sangue , Feminino , Estudos Prospectivos , Idoso , Recuperação de Função Fisiológica , Pessoa de Meia-Idade , Reabilitação do Acidente Vascular Cerebral , Biomarcadores/sangueRESUMO
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), discovered in December 2019 in Wuhan, China, caused the coronavirus disease 2019 (COVID-19). Due to the rate of spread of this virus, the World Health Organization, in March 2020, recognised COVID-19 as a worldwide pandemic. The disease is multisystemic with varying degrees of severity. Unfortunately, despite intensive research, the molecular changes caused by SARS-CoV-2 remain unclear. Mechanisms affected by the virus infection include endothelial dysfunction and angiogenesis. Similarly, the vaccines developed so far affect the process of angiogenesis, contributing to the development of undesirable effects on part of the cardiovascular system. The presented research aimed to investigate the impact of the SARS-CoV-2 infection and the Pfizer Comirnaty vaccine (BNT162b2) on the molecular aspect of angiogenesis. We found that convalescents vaccinated with one dose of BNT162b2 were characterised by higher MMP-7 (metalloproteinases 7) expression than non-vaccinated convalescents and healthy volunteers vaccinated with one dose of BNT162b2. Moreover, non-vaccinated convalescents showed increased mRNA expression of ADAMTS1 (ADAM metallopeptidase with thrombospondin type 1 motif 1) compared to healthy volunteers vaccinated with one dose of BNT162b2. In addition, we showed significant sex differences in the expression of MMP-7. In conclusion, the results of our study suggest a significant impact of SARS-CoV-2 infection and vaccination on the course of angiogenesis at the molecular level.
Assuntos
COVID-19 , Feminino , Humanos , Masculino , COVID-19/prevenção & controle , SARS-CoV-2 , Vacina BNT162 , Metaloproteinase 7 da Matriz , Vacinação , RNA Mensageiro/genéticaRESUMO
Multiple sclerosis (MS) is a chronic, autoimmune neurodegenerative disease affecting the central nervous system. It is a major cause of non-traumatic neurological disability among young adults in North America and Europe. This study focuses on neuroprotective genes (BDNF, NT4/5, SIRT1, HSP70, and HSP27). Gene expression and protein levels of these markers were compared between MS patients and healthy controls. Blood samples were collected from 42 patients with multiple sclerosis (MS) and 48 control subjects without MS. Quantitative real-time PCR was performed to measure the expression of specific genes. The samples were analyzed in duplicate, and the abundance of mRNA was quantified using the 2-ΔCt method. ELISA assay was used to measure the concentration of specific proteins in the plasma samples. The results show that a 3.5-fold decrease in the gene expression of BDNF corresponds to a 1.5-fold downregulation in the associated plasma protein concentration (p < 0.001). Similar trends were observed with NT-4 (five-fold decrease, slight elevation in protein), SIRT1 (two-fold decrease, two-fold protein decrease), HSP70 (four-fold increase, nearly two-fold protein increase), and HSP27 (four-fold increase, two-fold protein increase) (p < 0.001). This study reveals strong correlations between gene expression and protein concentration in MS patients, emphasizing the relevance of these neuroprotective markers in the disease.
Assuntos
Esclerose Múltipla , Doenças Neurodegenerativas , Adulto Jovem , Humanos , Esclerose Múltipla/genética , Esclerose Múltipla/metabolismo , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteínas de Choque Térmico HSP27 , Sirtuína 1/genética , RNA Mensageiro/genética , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSP70/metabolismo , Proteínas SanguíneasRESUMO
Immersive virtual therapy technology is a new method that uses head-mounted displays for rehabilitation purposes. It offers a realistic experience that puts the user in a virtual reality. This new type of therapy is used in the rehabilitation of stroke patients. Many patients after this disease have complications related to the upper extremities that limit independence in their everyday life, which affects the functioning of society. Conventional neurological rehabilitation can be supplemented by the use of immersive virtual therapy. The system allows patients with upper limb dysfunction to perform a motor and task-oriented training in virtual reality that is individually tailored to their performance. The complete immersion therapy itself is researched and evaluated by medical teams to determine the suitability for rehabilitation of the upper limb after a stroke. The purpose of this article is to provide an overview of the latest research (2019-2022) on immersive virtual reality with head-mounted displays using in rehabilitation of the upper extremities of stroke patients.
Assuntos
Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Reabilitação do Acidente Vascular Cerebral/métodos , Imersão , Extremidade Superior , Atividades Cotidianas , Recuperação de Função FisiológicaRESUMO
Multiple sclerosis (MS) is a chronic, immune-mediated disease and the leading cause of disability among young adults. MicroRNAs (miRNAs) are involved in the post-transcriptional regulation of gene expression. Of them, miR-155 is a crucial regulator of inflammation and plays a role in modulating the autoimmune response in MS. miR-155 is involved in blood-brain barrier (BBB) disruption via down-regulation of key junctional proteins under inflammatory conditions. It drives demyelination processes by contributing to, e.g., microglial activation, polarization of astrocytes, and down-regulation of CD47 protein and affecting crucial transcription factors. miR-155 has a huge impact on the development of neuropathic pain and indirectly influences a regulatory T (Treg) cell differentiation involved in the alleviation of pain hypersensitivity. This review also focused on neuropsychiatric symptoms appearing as a result of disease-associated stressors, brain atrophy, and pro-inflammatory factors. Recent studies revealed the role of miR-155 in regulating anxiety, stress, inflammation in the hippocampus, and treatment-resistant depression. Inhibition of miR-155 expression was demonstrated to be effective in preventing processes involved in the pathophysiology of MS. This review aimed to support the better understanding the great role of miR-155 dysregulation in various aspects of MS pathophysiology and highlight future perspectives for this molecule.
Assuntos
MicroRNAs/metabolismo , Esclerose Múltipla/metabolismo , Astrócitos , Autoimunidade , Regulação da Expressão Gênica , Humanos , Inflamação , MicroRNAs/imunologia , Esclerose Múltipla/genética , Esclerose Múltipla/imunologia , Esclerose Múltipla/psicologiaRESUMO
Epidemiological studies confirm a high risk of ischemic events in secondary-progressive multiple sclerosis (SP MS) patients, directly associated with an increased level of pro-thrombotic activity of platelets. Our work aimed to verify potential molecular abnormalities of the platelet P2Y12 receptor expression and functionality as a cause of an increased risk of thromboembolism observed in the course of MS. We have demonstrated an enhanced platelet reactivity in response to adenosine diphosphate (ADP) in SP MS relative to controls. We have also shown an increased mRNA expression for the P2RY12 gene in both platelets and megakaryocytes, as well as enhanced density of these receptors on the platelet surface. We postulate that one of the reasons for the elevated risk of ischemic events observed in MS may be a genetically or phenotypically reinforced expression of the platelet P2Y12 receptor. In order to analyze the effect of the PAR1 (protease activated receptor type 1) signaling pathway on the expression level of P2Y12, we also analyzed the correlation parameters between P2Y12 expression and the markers of platelet activation in MS induced by selective PAR1 agonist (thrombin receptor activating peptide-6, TRAP-6). Identifying the molecular base responsible for the enlarged pro-thrombotic activity of platelets in SP MS could contribute to the implementation of prevention and targeted treatment, reducing the development of cardiovascular disorders in the course of the disease.
Assuntos
Difosfato de Adenosina/metabolismo , Esclerose Múltipla/sangue , Ativação Plaquetária , Receptores Purinérgicos P2Y12/metabolismo , Células Cultivadas , Humanos , Esclerose Múltipla/genética , Esclerose Múltipla/metabolismo , Receptores Purinérgicos P2Y12/genética , Transdução de SinaisRESUMO
Multiple sclerosis (MS) is a debilitating neurodegenerative, highly heterogeneous disease with a variable course. The most common MS subtype is relapsing-remitting (RR), having interchanging periods of worsening and relative stabilization. After a decade, in most RR patients, it alters into the secondary progressive (SP) phase, the most debilitating one with no clear remissions, leading to progressive disability deterioration. Among the greatest challenges for clinicians is understanding disease progression molecular mechanisms, since RR is mainly characterized by inflammatory processes, while in SP, the neurodegeneration prevails. This is especially important because distinguishing RR from the SP subtype early will enable faster implementation of appropriate treatment. Currently, the MS course is not well-correlated with the biomarkers routinely used in clinical practice. Despite many studies, there are still no reliable indicators correlating with the disease stage and its activity degree. Circulating microRNAs (miRNAs) may be considered valuable molecules for the MS diagnosis and, presumably, helpful in predicting disease subtype. MiRNA expression dysregulation is commonly observed in the MS course. Moreover, knowledge of diverse miRNA panel expression between RRMS and SPMS may allow for deterring disability progression through successful treatment. Therefore, in this review, we address the current state of research on differences in miRNA panel expression between the phases.
Assuntos
Biomarcadores Tumorais/genética , MicroRNA Circulante/genética , Esclerose Múltipla Crônica Progressiva/diagnóstico , Recidiva Local de Neoplasia/diagnóstico , Animais , Diagnóstico Diferencial , Progressão da Doença , Humanos , Esclerose Múltipla Crônica Progressiva/genética , Recidiva Local de Neoplasia/genéticaRESUMO
The novel coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains a global challenge. Currently, there is some information on the consequences of COVID-19 infection in multiple sclerosis (MS) patients, as it is a newly discovered coronavirus, but its far-reaching effects on participation in neurodegenerative diseases seem to be significant. Recent cases reports showed that SARS-CoV-2 may be responsible for initiating the demyelination process in people who previously had no symptoms associated with any nervous system disorders. It is presently known that infection of SARS-CoV-2 evokes cytokine storm syndrome, which may be one of the factors leading to the acute cerebrovascular disease. One of the substantial problems is the coexistence of cerebrovascular disease and MS in an individual's life span. Epidemiological studies showed an enhanced risk of death rate from vascular disabilities in MS patients of approximately 30%. It has been demonstrated that patients with severe SARS-CoV-2 infection usually show increased levels of D-dimer, fibrinogen, C-reactive protein (CRP), and overactivation of blood platelets, which are essential elements of prothrombotic events. In this review, the latest knowledge gathered during an ongoing pandemic of SARS-CoV-2 infection on the neurodegeneration processes in MS is discussed.
Assuntos
COVID-19/complicações , Esclerose Múltipla/complicações , Doenças Neurodegenerativas/etiologia , Animais , COVID-19/patologia , COVID-19/virologia , Síndrome da Liberação de Citocina/etiologia , Síndrome da Liberação de Citocina/patologia , Síndrome da Liberação de Citocina/virologia , Humanos , Esclerose Múltipla/patologia , Esclerose Múltipla/virologia , Doenças Neurodegenerativas/patologia , Doenças Neurodegenerativas/virologia , SARS-CoV-2/isolamento & purificação , Trombose/etiologia , Trombose/patologiaRESUMO
Several key issues impact the clinical practice of stroke rehabilitation including a patient's medical history, stroke experience, the potential for recovery, and the selection of the most effective type of therapy. Until clinicians have answers to these concerns, the treatment and rehabilitation are rather intuitive, with standard procedures carried out based on subjective estimations using clinical scales. Therefore, there is a need to find biomarkers that could predict brain recovery potential in stroke patients. This review aims to present the current state-of-the-art stroke recovery biomarkers that could be used in clinical practice. The revision of biochemical biomarkers has been developed based on stroke recovery processes: angiogenesis and neuroplasticity. This paper provides an overview of the biomarkers that are considered to be ready-to-use in clinical practice and others, considered as future tools. Furthermore, this review shows the utility of biomarkers in the development of the concept of personalized medicine. Enhancing brain neuroplasticity and rehabilitation facilitation are crucial concerns not only after stroke, but in all central nervous system diseases.
Assuntos
Neovascularização Fisiológica , Plasticidade Neuronal , Medicina de Precisão , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral/metabolismo , Biomarcadores/metabolismo , HumanosRESUMO
Malnutrition is a serious problem in post-stroke patients. Importantly, it intensifies with hospitalization, and is related to both somatic and psychological reasons, as well as is associated with the insufficient knowledge of people who accompany the patient. Malnutrition is a negative prognostic factor, leading to a reduction in the quality of life. Moreover, this condition significantly extends hospitalization time, increases the frequency of treatment in intensive care units, and negatively affects the effectiveness of rehabilitation. Obtaining growing data on the therapeutic effectiveness of new compounds of natural origin is possible through the use of pharmacodynamic and analytical methods to assess their therapeutic properties. The proper supply of nutrients, as well as compounds of natural origin, is an important element of post-stroke therapy, due to their strong antioxidant, anti-inflammatory, neuroprotective and neuroplasticity enhancing properties. Taking the above into account, in this review we present the current state of knowledge on the benefits of using selected substances of natural origin in patients after cerebral stroke.
Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Produtos Biológicos/farmacologia , Suplementos Nutricionais , Desnutrição/prevenção & controle , Neuroproteção , Acidente Vascular Cerebral/tratamento farmacológico , Animais , HumanosRESUMO
Cognitive function decline is strictly related to age, resulting in the loss of the ability to perform daily behaviors and is a fundamental clinical neurodegeneration symptom. It has been proven that an adequate diet, comprehensive nutrition, and a healthy lifestyle may significantly inhibit neurodegenerative processes, improving cognitive functions. Therefore, intensive research has been conducted on cognitive-enhancing treatment for many years, especially with substances of natural origin. There are several intervention programs aimed at improving cognitive functions in elderly adults. Cognitive functions depend on body weight, food consumed daily, the quality of the intestinal microflora, and the supplements used. The effectiveness in the prevention of dementia is particularly high before the onset of the first symptoms. The impact of diet and nutrition on age-associated cognitive decline is becoming a growing field as a vital factor that may be easily modified, and the effects may be observed on an ongoing basis. The paper presents a review of the latest preclinical and clinical studies on the influence of natural antioxidants on cognitive functions, with particular emphasis on neurodegenerative diseases. Nevertheless, despite the promising research results in animal models, the clinical application of natural compounds will only be possible after solving a few challenges.
Assuntos
Envelhecimento , Antioxidantes/uso terapêutico , Produtos Biológicos/uso terapêutico , Transtornos Cognitivos/tratamento farmacológico , Transtornos Cognitivos/etiologia , Doenças Neurodegenerativas/complicações , Animais , Antioxidantes/farmacologia , Produtos Biológicos/farmacologia , Ensaios Clínicos como Assunto , Cognição/efeitos dos fármacos , Transtornos Cognitivos/diagnóstico , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/etiologia , Suplementos Nutricionais , Avaliação Pré-Clínica de Medicamentos , Humanos , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/etiologia , Resultado do TratamentoRESUMO
Multiple sclerosis (MS) and Devic's disease (NMO; neuromyelitis optica) are autoimmune, inflammatory diseases of the central nervous system (CNS), the etiology of which remains unclear. It is a serious limitation in the treatment of these diseases. The resemblance of the clinical pictures of these two conditions generates a partial possibility of introducing similar treatment, but on the other hand, a high risk of misdiagnosis. Therefore, a better understanding and comparative characterization of the immunopathogenic mechanisms of each of these diseases are essential to improve their discriminatory diagnosis and more effective treatment. In this review, special attention is given to Th17 cells and Th17-related cytokines in the context of their potential usefulness as discriminatory markers for MS and NMO. The discussed results emphasize the role of Th17 immune response in both MS and NMO pathogenesis, which, however, cannot be considered without taking into account the broader perspective of immune response mechanisms.
Assuntos
Esclerose Múltipla/imunologia , Neuromielite Óptica/imunologia , Células Th17/imunologia , Imunidade Adaptativa/imunologia , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/imunologia , Biomarcadores , Citocinas/imunologia , Citocinas/metabolismo , Diagnóstico Diferencial , Humanos , Esclerose Múltipla/diagnóstico , Neuromielite Óptica/diagnóstico , Células Th17/fisiologiaRESUMO
Background and Objectives: Multiple Sclerosis (MS) is a demyelinating disease of the central nervous system (CNS), most commonly characterized by balance dysfunction, fatigue syndrome and cognitive impairment. The goal of our study was to determine the association between cognitive functions and static posture control. Materials and Methods: The research group consisted of 76 randomized MS patients (ICDG 35.0) hospitalized at the Neurological Rehabilitation Clinic of the Medical University of Lodz. This group was divided into three subgroups according to the cognitive assessment based on the Mini Mental State Examination (MMSE) for patients over 65 years of age and the Montreal Cognitive Assessment (MoCA) under the age of 65. Fatigue syndrome was assessed using the Fatigue Severity Scale (FSS), and postural stability using a stabilometric platform. Results: The men demonstrated poorer stabilometric platform measurements than the women. Statistically significant differences were observed between patients without dysfunction and severe cognitive impairment. The results of the stabilometric platform were found to correlate with body mass index in all three groups of patients (Spearman's test). Conclusions: Body mass index and cognition have impact on postural stability in MS patients with moderate disability and fatigue syndrome.
Assuntos
Transtornos Cognitivos , Disfunção Cognitiva , Esclerose Múltipla , Cognição , Disfunção Cognitiva/etiologia , Feminino , Humanos , Masculino , Testes de Estado Mental e Demência , Esclerose Múltipla/complicaçõesRESUMO
Epidemiological studies confirm the high risk of ischemic events in multiple sclerosis (MS) that are associated with increased pro-thrombotic activity of blood platelets. The most potent physiological platelet agonist is thrombin, which activates platelets via cleavage of specific protease-activated receptors (PARs). Our current study is aimed to determine the potential genetics and proteomic abnormalities of PAR1 in both platelets and megakaryocytes, which may have thromboembolic consequences in the course of MS. The obtained results were correlated with the expression level of platelet and megakaryocyte transcripts for APOA1 and A2M genes encoding atherosclerosis biomarkers: apolipoprotein A1 (ApoA1) and α-2-macroglobulin (α2M), respectively. Moreover, PAR1 functionality in MS platelets was assessed by flow cytometry, determining the level of platelet-platelet and platelet-leukocyte aggregates, platelet microparticles and surface expression of P-selectin. As a PAR1 agonist, the synthetic TRAP-6 peptide was used, which made it possible to achieve platelet activation in whole blood without triggering clotting. Comparative analyses showed an elevated level of platelet activation markers in the blood of MS patients compared to controls. The mRNA expression of gene coding α2M was upregulated, whilst ApoA1 was down-regulated, both in platelets and megakaryocytes from MS patients. Furthermore, we observed an increase in both mRNA expression and surface density of PAR1 in platelets and megakaryocytes in MS compared to controls. Both the level of platelet activation markers and PAR1 expression showed a high correlation with the expression of transcripts for APOA1 and A2M genes.
Assuntos
Plaquetas/patologia , Esclerose Múltipla Crônica Progressiva/sangue , Receptor PAR-1/metabolismo , Trombina/metabolismo , Trombose/patologia , Apolipoproteína A-I/genética , Apolipoproteína A-I/metabolismo , Aterosclerose/sangue , Aterosclerose/complicações , Aterosclerose/genética , Aterosclerose/patologia , Biomarcadores/metabolismo , Feminino , Regulação da Expressão Gênica , Humanos , Masculino , Megacariócitos/metabolismo , Pessoa de Meia-Idade , Esclerose Múltipla Crônica Progressiva/complicações , alfa 2-Macroglobulinas Associadas à Gravidez/genética , alfa 2-Macroglobulinas Associadas à Gravidez/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptor PAR-1/genéticaRESUMO
One of the most important goals in the treatment of demyelinating diseases such as multiple sclerosis (MS) is, in addition to immunomodulation, reconstruction of the lost myelin sheath. The modulator of the central nervous system myelination is the metabotropic receptor coupled to the G-protein: GPR17. GPR17 receptors are considered to be sensors of local damage to the myelin sheath, and play a role in the reconstruction and repair of demyelinating plaques caused by ongoing inflammatory processes. GPR17 receptors are present on nerve cells and precursor oligodendrocyte cells. Under physiological conditions, they are responsible for the differentiation and subsequent maturation of oligodendrocytes, while under pathological conditions (during damage to nerve cells), their expression increases to become mediators in the demyelinating processes. Moreover, they are essential not only in both the processes of inducing damage and the death of neurons, but also in the local repair of the damaged myelin sheath. Therefore, GPR17 receptors may be recognized as the potential goal in creating innovative therapies for the treatment of the neurodegenerative process in MS, based on the acceleration of the remyelination processes. This review examines the role of GRP17 in pathomechanisms of MS development.
Assuntos
Esclerose Múltipla/metabolismo , Esclerose Múltipla/patologia , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/patologia , Receptores Acoplados a Proteínas G/metabolismo , Animais , Biomarcadores/metabolismo , Humanos , Esclerose Múltipla/genética , Doenças Neurodegenerativas/genética , Receptores Acoplados a Proteínas G/genética , Remielinização/genética , Remielinização/fisiologiaRESUMO
Metformin, a synthetic derivative of guanidine, is commonly used as an oral antidiabetic agent and is considered a multi-vector application agent in the treatment of other inflammatory diseases. Recent studies have confirmed the beneficial effect of metformin on immune cells, with special emphasis on immunological mechanisms. Multiple Sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) characterized by various clinical courses. Although the pathophysiology of MS remains unknown, it is most likely a combination of disturbances of the immune system and biochemical pathways with a disruption of blood-brain barrier (BBB), and it is strictly related to injury of intracerebral blood vessels. Metformin has properties which are greatly desirable for MS therapy, including antioxidant, anti-inflammatory or antiplatelet functions. The latest reports relating to the cardiovascular disease confirm an increased risk of ischemic events in MS patients, which are directly associated with a coagulation cascade and an elevated pro-thrombotic platelet function. Hence, this review examines the potential favourable effects of metformin in the course of MS, its role in preventing inflammation and endothelial dysfunction, as well as its potential antiplatelet role.
Assuntos
Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Animais , Ensaios Clínicos como Assunto , Hemostasia/efeitos dos fármacos , Humanos , Hipoglicemiantes/farmacologia , Metformina/farmacologiaRESUMO
Epidemiological studies indicate a high risk of stroke, heart failure and myocardial infarction in patients with multiple sclerosis, especially in its secondary progressive (SPMS) phase. Some ischaemic events are directly associated with abnormal platelet functions and their prothrombotic activity. Recent reports, including this study, confirm the increased activation of circulating platelets in SPMS, and also show increased platelet reactivity, among other responses, as well as strong aggregation. In this current study, we conducted a comparative analysis of the platelet proteome in SPMS patients and in healthy controls, to demonstrate the quantitative and qualitative differences likely to affect functional changes observed in SPMS. During densitometry evaluation of 2-D fluorescence difference gel electrophoresis, we observed differences between the electrophoretic patterns of SPMS platelets and the control samples. To determine a detailed characterisation of the proteome changes in the SPMS patients' blood platelets, in the next stage, we performed mass spectrometry of selected spots and indicated the increased presence of four proteins (fibrinogen, α-2 macroglobulin, septin-14 and tubulin ß-1 chain). The most important of these is the increased amount of prothrombotic protein, fibrinogen, which seems to confirm the accuracy of the imaging and potentially explains the increased risk of platelet-origin thrombotic events. This study provides new knowledge of the potential existence of the molecular mechanisms responsible for the acceleration of the platelet pro-coagulant function in SPMS. This can help to identify new targets for therapy, which can then be used not only in the second stage of the disease.
Assuntos
Plaquetas/metabolismo , Fibrinogênio/metabolismo , Esclerose Múltipla/sangue , Proteoma/metabolismo , Sequência de Aminoácidos , Feminino , Fibrinogênio/química , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Purpose The aim of this study was to evaluate the level of burnout syndrome and quality of life (QoL) among Polish massage therapists, and determine their relationship with sociodemographic and work-related variables. Methods A group of 43 participants aged 28-63, who were blind or poor-sighted were recruited for the study. They were surveyed with sociodemographic data questionnaire and the Polish versions of the Maslach Burnout Inventory-General Survey and WHOQOL-BREF. Results The overall level of exhaustion was 6.79 ± 4.45, cynicism was estimated at 7.30 ± 3.43, and professional efficacy was 23.3 ± 5.44. Regarding QoL, the psychological domain was the highest (73.6 ± 10.0), while the physical domain was the lowest (61.1 ± 6.94). None of the sociodemographic variables or occupational factors had any statistical relationship with any burnout subscale. Significant correlations were found between the psychological domain of QoL and marital status (H = 6.570; p = 0.037), years of practice (ρ = 0.315; t = 2.124; p = 0.039), hours of practice per week (ρ = 0.364; t = 2.505; p = 0.016) and private practice (z = 2.393; p = 0.017). Significant relationships were found between the environmental domain of QoL and the place of residence (H = 5.977; p = 0.050) and between hours of practice per week (ρ = 0.335; t = 2.276; p = 0.028). A significant positive correlation was noted between professional efficacy and the social relationship domain (ρ = 0.306; t = 2.056; p = 0.046). Conclusion Job activity plays a crucial function in the psychosocial rehabilitation of massage therapists with visual impairment. This was confirmed by the low risk of burnout, and the psychological domain being the highest of QoL.