RESUMO
Synaptic plasticity, including long-term potentiation (LTP) and long-term depression (LTD), is an essential phenomenon in memory formation as well as maintenance along with many other cognitive functions, such as those needed for coping with external stimuli. Synaptic plasticity consists of gradual changes in the biochemistry and morphology of pre- and postsynaptic neurons, particularly in the hippocampus. Consuming marijuana as a primary source of exocannabinoids immediately impairs attention and working memory-related tasks. Evidence regarding the effects of cannabinoids on LTP and memory is contradictory. While cannabinoids can affect a variety of specific cannabinoid receptors (CBRs) and nonspecific receptors throughout the body and brain, they exert miscellaneous systemic and local cerebral effects. Given the increasing use of cannabis, mainly among the young population, plus its potential adverse long-term effects on learning and memory processes, it could be a future global health challenge. Indeed, the impact of cannabinoids on memory is multifactorial and depends on the dosage, timing, formula, and route of consumption, plus the background complex interaction of the endocannabinoids system with other cerebral networks. Herein, we review how exogenously administrated organic cannabinoids, CBRs agonists or antagonists, and endocannabinoids can affect LTP and synaptic plasticity through various receptors in interaction with other cerebral pathways and primary neurotransmitters.
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Canabinoides , Potenciação de Longa Duração , Memória , Plasticidade Neuronal , Canabinoides/farmacologia , Canabinoides/metabolismo , Humanos , Plasticidade Neuronal/efeitos dos fármacos , Animais , Potenciação de Longa Duração/efeitos dos fármacos , Memória/efeitos dos fármacos , Endocanabinoides/metabolismo , Endocanabinoides/farmacologia , Receptores de Canabinoides/metabolismo , Depressão Sináptica de Longo Prazo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/efeitos dos fármacosRESUMO
BACKGROUND: This study aimed to evaluate the reactogenicity effects of COVID-19 vaccines, used in Iran. METHODS: At least 1000 people were followed up with phone calls or self-report in a mobile application within 7 days after vaccination. Local and systemic reactogenicities were reported overall and by subgroups. RESULTS: The presence of one or more local and systemic adverse effects after the first dose of vaccines was 58.9% [(95% Confidence Intervals): 57.5-60.3)] and 60.5% (59.1-61.9), respectively. These rates were reduced to 53.8% (51.2-55.0) and 50.8% (48.8-52.7) for the second dose. The most common local adverse effect reported for all vaccines was pain in the injection site. During the first week after the first dose of vaccines, the frequency of the pain for Sinopharm, AZD1222, Sputnik V, and Barekat was 35.5%, 86.0%, 77.6%, and 30.9%, respectively. The same rates after the second dose were 27.3%, 66.5%, 63.9%, and 49.0%. The most common systemic adverse effect was fatigue. In the first dose, it was 30.3% for Sinopharm, 67.4% for AZD1222, 47.6% for Sputnik V, and 17.1% for Barekat. These rates were reduced to 24.6%, 37.1%, 36.5%, and 19.5%, in the second dose of vaccines. AZD1222 had the highest local and systemic adverse effects rates. The odds ratio of local adverse effects of the AZD1222 vaccine compared to the Sinopharm vaccine were 8.73 (95% CI 6.93-10.99) in the first dose and 4.14 (95% CI 3.32-5.17) in the second dose. Barekat and Sinopharm had the lowest frequency of local and systemic adverse effects. Compared to Sinopharm, systemic adverse effects were lower after the first dose of Barekat (OR = 0.56; 95% CI 0.46-0.67). Reactogenicity events were higher in women and younger people. Prior COVID-19 infection increased the odds of adverse effects only after the first dose of vaccines. CONCLUSIONS: Pain and fatigue were the most common reactogenicities of COVID-19 vaccination. Reactogenicities were less common after the second dose of the vaccines. The adverse effects of AZD1222 were greater than those of other vaccines.
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COVID-19 , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Vacinas , Feminino , Humanos , ChAdOx1 nCoV-19 , Irã (Geográfico) , Vacinas contra COVID-19 , Vacinação , Fadiga , DorRESUMO
Mephedrone, a synthetic derivative of cathinone, is a commonly used psychoactive substance. Our previous study showed that exposure to mephedrone during pegnancy induced antiproliferative and pro-apoptotic effects in hippocampus of mice delivered pups. However, its effects on neural stem/progenitor cells (NS/PC) remain unexplored. The aim of this study is to investigate the effects of mephedrone exposure on the proliferation, differentiation, and apoptosis of rat embryonic NS/PC. NS/PC were isolated from rat fetal ganglionic eminence region at embryonic day 14.5. The effects of mephedrone on cell proliferation, neurosphere formation (colonies of NS/PC), neuronal differentiation, and apoptosis of NS/PC were assessed using MTT, immunocytochemistry, and flow cytometry. Mephedrone at concentrations of 20-640 µM significantly decreased the proliferation of NS/PC, induced cell cycle arrest, and enhanced the percent of apoptotic and necrotic cells. Neurosphere assays revealed a significant reduction in the number and diameter of neurosphere-forming cells. In addition, mephedrone significantly decreased the expressions of DCX and NeuN neuronal markers. Taken together, our results suggeste that exposure to mephedrone decreases the viability and neuronal differentiation of embryonic NS/PC. This study showed that mephedrone exposure during fetal or neonatal life may impair neurogenesis and subsequent brain development.
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Células-Tronco Neurais , Ratos , Camundongos , Animais , Neurogênese , Neurônios , Apoptose , Diferenciação Celular , Proliferação de Células , Células CultivadasRESUMO
Objective: To investigate the incidence of coronavirus disease 2019 (COVID-19) cases, hospitalizations and deaths in Iranians vaccinated with either AZD1222 Vaxzevria, CovIran® vaccine, SARS-CoV-2 Vaccine (Vero Cell), Inactivated (lnCoV) or Sputnik V. Methods: We enrolled individuals 18 years or older receiving their first COVID-19 vaccine dose between April 2021 and January 2022 in seven Iranian cities. Participants completed weekly follow-up surveys for 17 weeks (25 weeks for AZD1222) to report their COVID-19 status and hospitalization. We used Cox regression models to assess risk factors for contracting COVID-19, hospitalization and death. Findings: Of 89 783 participants enrolled, incidence rates per 1 000 000 person-days were: 528.2 (95% confidence interval, CI: 514.0-542.7) for contracting COVID-19; 55.8 (95% CI: 51.4-60.5) for hospitalization; and 4.1 (95% CI: 3.0-5.5) for death. Compared with SARS-CoV-2 Vaccine (Vero Cell), hazard ratios (HR) for contracting COVID-19 were: 0.70 (95% CI: 0.61-0.80) with AZD1222; 0.73 (95% CI: 0.62-0.86) with Sputnik V; and 0.73 (95% CI: 0.63-0.86) with CovIran®. For hospitalization and death, all vaccines provided similar protection 14 days after the second dose. History of COVID-19 protected against contracting COVID-19 again (HR: 0.76; 95% CI: 0.69-0.84). Diabetes and respiratory, cardiac and renal disease were associated with higher risks of contracting COVID-19 after vaccination. Conclusion: The rates of contracting COVID-19 after vaccination were relatively high. SARS-CoV-2 Vaccine (Vero Cell) provided lower protection against COVID-19 than other vaccines. People with comorbidities had higher risks of contracting COVID-19 and hospitalization and should be prioritized for preventive interventions.
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COVID-19 , Vacinas , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19 , ChAdOx1 nCoV-19 , Estudos de Coortes , Hospitalização , Humanos , Irã (Geográfico)/epidemiologia , SARS-CoV-2 , VacinaçãoRESUMO
BACKGROUND AND OBJECTIVE: Dentate gyrus (DG) has a high density of 5-HT1A receptors. It has neural nitric oxide synthase (nNOS), which is involved in neural excitability. The purpose of this study was to investigate the role of 5-HT1A receptors and nNOS of DG in perforant path kindling model of epilepsy. MATERIAL AND METHODS: To achieve this purpose, a receptor antagonist (WAY100635, 0.1 mg/kg, intracerebroventricular, i.c.v) and neuronal nitric oxide synthase inhibitor (7-NI, 15 mg/kg, intraperitoneal, i.p.) were injected during kindling aquisition. Adult male Wistar rats (280 ± 20 g) were used in this study Animals were kindled through the daily administration of brief electrical stimulations (10 stimulations per day) to the perforant pathway. Field potential recordings were performed for 20 min in DG beforehand. Additionally, glial fibrillary acidic protein (GFAP) expression rate in the DG was determined using immunohistochemistry as a highly specific marker for glia. RESULTS: WAY100635 (0.1 mg/kg) significantly attenuated the kindling threshold compared to the kindled + vehicle group (P < 0.001). The co-administration of WAY100635 with 7-NI, exerted a significant anticonvulsive effect. Furthermore, the slope of field Excitatory Post Synaptic Potentials (fEPSP) at the end of 10 days in the kindled + 7-NI + WAY100635 group was significantly lower than in the kindled + vehicle group (P < 0.001). Furthermore, immunohistochemistry showed that the density of GAFP+ cells in the kindled + 7-NI + WAY100635 group was significantly higher than in the kindled + vehicle group (P < 0.001). CONCLUSION: Our data demonstrate that antagonists of 5-HT1A receptors have proconvulsive effects and that astrocyte cells are involved in this process, while nNOS has an inhibitory effect on neuronal excitability.
Assuntos
Hipocampo , Excitação Neurológica , Animais , Hipocampo/metabolismo , Masculino , Óxido Nítrico Sintase Tipo I/metabolismo , Via Perfurante/metabolismo , Ratos , Ratos WistarRESUMO
BACKGROUND: New vaccines that are initially approved in clinical trials are not completely free of risks. Systematic vaccine safety surveillance is required for ensuring safety of vaccines. This study aimed to provide a protocol for safety monitoring of COVID-19 vaccines, including Sputnik V, Sinopharm (BBIBP-CorV), COVIran Barekat, and AZD1222. METHODS: This is a prospective cohort study in accordance with a template provided by the World Health Organization. The target population includes citizens of seven cities in Iran who have received one of the available COVID-19 vaccines according to the national instruction on vaccination. The participants are followed for three months after they receive the second dose of the vaccine. For each type of vaccine, 30,000 people will be enrolled in the study of whom the first 1,000 participants are in the reactogenicity subgroup. The reactogenicity outcomes will be followed seven days after vaccination. Any hospitalization, COVID-19 disease, or other minor outcomes will be investigated in weekly follow-ups. The data are gathered through self-reporting of participants in a mobile application or phone calls to them. The study outcomes may be investigated for the third and fourth doses of vaccines. Other long-term outcomes may also be investigated after the expansion of the follow-up period. We have planned to complete data collection for the current objectives by the end 2022. DISCUSSION: The results of this study will be published in different articles. A live dashboard is also available for managers and policymakers. All data will be available on reasonable requests from the corresponding author.The use of the good and comprehensive guidelines provided by WHO, along with the accurate implementation of the protocol and continuous monitoring of the staff performance are the main strengths of this study which may be very useful for policymaking about COVID-19 vaccination.
Assuntos
Vacinas contra COVID-19 , COVID-19 , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , ChAdOx1 nCoV-19 , Humanos , Irã (Geográfico)/epidemiologia , Estudos Prospectivos , Projetos de Pesquisa , SARS-CoV-2 , Vacinação/efeitos adversosRESUMO
This study aims to improve the curcumin bio-stability and brain permeability by loading in bare niosome (BN) and chitosan-coated niosome (ChN). Span 60, tween 60, and cholesterol were optimized as niosome shell components to attain the highest encapsulation efficiency (EE), besides the lowest particle size, using the mixture design method. The resulting optimized BN had a mean diameter of 80 ± 0.2 nm and surface charge of -31 ± 0.1 mv, which changed to 85 ± 0.15 nm and 35 ± 0.12 mv, respectively, after applying the chitosan layer. The EE% in bare niosome were about 80 ± 0.2, which changed to 82 ± 0.21 in ChN. The optimized formulation displayed sustained release, following the Hixson-Crowell model.Wistar rats were subjected to intraperitoneal injection (i.p.) of BN and ChN to evaluate the blood-brain barrier permeability of the curcumin. In this regard, ChN significantly increased curcumin concentration in different parts of the liver, plasma, and central nervous system (cerebral cortex, cerebellum, and stratum), compared with BN. Altogether, our results showed that ChN could be used as a promising delivery system for the treatment of some neurological diseases such as Alzheimer's.
Assuntos
Quitosana , Curcumina , Nanopartículas , Animais , Barreira Hematoencefálica , Curcumina/farmacologia , Portadores de Fármacos , Excipientes , Lipossomos , Tamanho da Partícula , Ratos , Ratos WistarRESUMO
In this study, chitosan-coated niosome (ChN) was utilised for bioavailability enhancement of curcumin (Cn) and boswellic acids (BAs). The bare niosome (BN) was prepared by the heating method and optimised by using the mixture design procedure. Physicochemical stability, as well as the in vitro release, and bioavailability of Cn and BAs in BN and ChN were studied. The optimised BN had a mean diameter of 70.00 ± 0.21 nm and surface charge of -31.00 ± 0.25 mv, which changed to 60.01 ± 0.20 nm and +40.00 ± 0, respectively, in ChN. In-vitro digestion study revealed chitosan layer augmented the bioavailability of Cn and BAs to 79.02 ± 0.13 and 81 ± 0.10, respectively. The chitosan layer obviously improved the physical stability of Cn and BA in the niosome vehicle, by means of vesicle size, zeta potential, and encapsulation efficiency. The ChN was considered to be promising delivery system for increasing the bioavailability of Cn and BAs.
Assuntos
Quitosana , Curcumina , Nanopartículas , Digestão , Portadores de Fármacos , Lipossomos , Tamanho da PartículaRESUMO
Among different types of mechanisms involved in neurological disorders, neuroinflammation links initial insults to secondary injuries and triggers some chronic outcomes, for example, neurodegenerative disorders. Thus, anti-inflammatory substances can be targeted as a novel therapeutic option for translational and clinical research to improve brain disease outcomes. In this review, we propose to introduce a new insight into the anti-inflammatory effects of mesenchymal stem cells (MSCs) as the most frequent source for stem cell therapy in neurological diseases. Our insight incorporates a bystander effect of these stem cells in modulating inflammation and microglia/macrophage polarization through exosomes. Exosomes are nano-sized membrane vesicles that carry cell-specific constituents, including protein, lipid, DNA, and RNA. microRNAs (miRNAs) have recently been detected in exosomes that can be taken up by other cells and affect the behavior of recipient cells. In this article, we outline and highlight the potential use of exosomal miRNAs derived from MSCs for inflammatory pathways in the context of neurological disorders. Furthermore, we suggest that focusing on exosomal miRNAs derived from MSCs in the course of neuroinflammatory pathways in the future could reveal their functions for diverse neurological diseases, including brain injuries and neurodegenerative diseases. It is hoped that this study will contribute to a deep understanding of stem cell bystander effects through exosomal miRNAs.
Assuntos
Exossomos/genética , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/genética , Doenças Neurodegenerativas/metabolismo , Doenças Neuroinflamatórias/tratamento farmacológico , Animais , Exossomos/metabolismo , Humanos , Inflamação/tratamento farmacológico , Inflamação/genética , Inflamação/metabolismo , MicroRNAs/metabolismo , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neuroinflamatórias/genéticaRESUMO
This study was designed to evaluate whether severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can directly target the central nervous system (CNS). We present four patients suffering from the loss of consciousness and seizure during the clinical course of COVID-19 infection. In addition to positive nasopharyngeal swab tests, SARS-CoV-2 has been detected in their cerebrospinal fluid. This report indicates the neuroinvasive potential of SARS-CoV-2, suggesting the ability of this virus to spread from the respiratory tract to the CNS.
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COVID-19/complicações , Líquido Cefalorraquidiano/virologia , SARS-CoV-2/isolamento & purificação , Convulsões/virologia , Síndrome Respiratória Aguda Grave/virologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
5-Aminolevulinic acid (5-ALA) is a naturally occurring non-proteinogenic amino acid, which contributes to the diagnosis and therapeutic approaches of various cancers, including glioblastoma (GBM). In the present study, we aimed to investigate whether 5-ALA exerted cytotoxic effects on GBM cells. We assessed cell viability, apoptosis rate, mRNA expressions of various apoptosis-related genes, generation of reactive oxygen species (ROS), and migration ability of the human U-87 malignant GBM cell line (U87MG) treated with 5-ALA at different doses. The half-maximal inhibitory concentration of 5-ALA on U87MG cells was 500 µg/mL after 7 days; 5-ALA was not toxic for human optic cells and NIH-3T3 cells at this concentration. The application of 5-ALA led to a significant increase in apoptotic cells, enhancement of Bax and p53 expressions, reduction in Bcl-2 expression, and an increase in ROS generation. Furthermore, the application of 5-ALA increased the accumulation of U87MG cells in the SUB-G1 population, decreased the expression of cyclin D1, and reduced the migration ability of U87MG cells. Our data indicate the potential cytotoxic effects of 5-ALA on U87MG cells. Further studies are required to determine the spectrum of the antitumor activity of 5-ALA on GBM.
Assuntos
Ácido Aminolevulínico/farmacologia , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias Encefálicas/tratamento farmacológico , Movimento Celular/efeitos dos fármacos , Glioblastoma/tratamento farmacológico , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ciclina D1/genética , Ciclina D1/metabolismo , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glioblastoma/metabolismo , Humanos , Camundongos , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismoRESUMO
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can enter the central nervous system and cause several neurological manifestations. Data from cerebrospinal fluid analyses and postmortem samples have been shown that SARS-CoV-2 has neuroinvasive properties. Therefore, ongoing studies have focused on mechanisms involved in neurotropism and neural injuries of SARS-CoV-2. The inflammasome is a part of the innate immune system that is responsible for the secretion and activation of several pro-inflammatory cytokines, such as interleukin-1ß, interleukin-6, and interleukin-18. Since cytokine storm has been known as a major mechanism followed by SARS-CoV-2, inflammasome may trigger an inflammatory form of lytic programmed cell death (pyroptosis) following SARS-CoV-2 infection and contribute to associated neurological complications. We reviewed and discussed the possible role of inflammasome and its consequence pyroptosis following coronavirus infections as potential mechanisms of neurotropism by SARS-CoV-2. Further studies, particularly postmortem analysis of brain samples obtained from COVID-19 patients, can shed light on the possible role of the inflammasome in neurotropism of SARS-CoV-2.
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COVID-19/metabolismo , Sistema Nervoso Central/metabolismo , Inflamassomos/metabolismo , Piroptose/fisiologia , SARS-CoV-2/metabolismo , Encéfalo/imunologia , Encéfalo/metabolismo , COVID-19/imunologia , Sistema Nervoso Central/imunologia , Humanos , Inflamassomos/imunologia , SARS-CoV-2/imunologiaRESUMO
Neural tissue engineering has been introduced as a novel therapeutic strategy for traumatic brain injury (TBI). Transplantation of mesenchymal stem cells (MSCs) has been demonstrated to improve functional outcome of brain injury, and RADA4GGSIKVAV (R-GSIK), a self-assembling nano-peptide scaffold, has been suggested to promote the behavior of stem cells. This study was designed to determine the ability of the R-GSIK scaffold in supporting the effects of MSCs on motor function activity and inflammatory responses in an experimental TBI model. A significant recovery of motor function was observed in rats that received MSCs+R-GSIK compared with the control groups. Further analysis showed a reduction in the number of reactive astrocytes and microglial cells in the MSCs and MSCs+R-GSIK groups compared with the control groups. Furthermore, western blot analysis indicated a significant reduction in pro-inflammatory cytokines, such as TLR4, TNF, and IL6, in the MSCs and MSCs+R-GSIK groups compared with the TBI, vehicle, and R-GSIK groups. Overall, this study strengthens the idea that the co-transplantation of MSCs with R-GSIK can increase functional outcomes by preparing a beneficial environment. This improvement may be explained by the immunomodulatory effects of MSCs and the self-assembling nano-scaffold peptide.
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Lesões Encefálicas Traumáticas/terapia , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/citologia , Peptídeos/administração & dosagem , Alicerces Teciduais/normas , Animais , Lesões Encefálicas Traumáticas/patologia , Diferenciação Celular/fisiologia , Modelos Animais de Doenças , Masculino , Ratos , Ratos WistarRESUMO
Alzheimer's disease (AD) is described as cognitive and memory impairments with a sex-related epidemiological profile, affecting two times more women than men. There is emerging evidence that alternations in the hippocampal neurogenesis occur at the early stage of AD. Therapies that may effectively slow, stop, or regenerate the dying neurons in AD are being extensively investigated in the last few decades, but none has yet been found to be effective. The regulation of endogenous neurogenesis is one of the main therapeutic targets for AD. Mounting evidence indicates that the neurosteroid estradiol (17ß-estradiol) plays a supporting role in neurogenesis, neuronal activity, and synaptic plasticity of AD. This effect may provide preventive and/or therapeutic approaches for AD. In this article, we discuss the molecular mechanism of potential estradiol modulatory action on endogenous neurogenesis, synaptic plasticity, and cognitive function in AD.
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Doença de Alzheimer/fisiopatologia , Doença de Alzheimer/psicologia , Cognição/efeitos dos fármacos , Estradiol/farmacologia , Neurogênese/efeitos dos fármacos , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Animais , Modelos Animais de Doenças , Hipocampo/efeitos dos fármacos , Hipocampo/fisiologia , Humanos , Neurogênese/fisiologia , Plasticidade Neuronal/efeitos dos fármacos , Plasticidade Neuronal/genética , Neurônios/efeitos dos fármacos , Neurônios/fisiologiaRESUMO
AIMS: This study aimed at investigating the impact of Dicrocoelium ova on experimental autoimmune encephalomyelitis (EAE) treatment in C57BL6 mice. METHODS AND RESULTS: Twenty-eight C57BL/6 mice were assigned into four groups as PBS, prophylaxis (P), treatment1 (T1) and treatment2 (T2). Prior to induction of EAE in prophylaxis group and on days 7 and 18 in T1 and T2 groups, respectively, Dicrocoelium eggs were injected intraperitoneally to each mouse. The clinical score, weight changes and incidence time of EAE were recorded. IFN-γ and IL-4 expression is quantified on spleen cells. Also, histopathological study by (H&E) and Toluidine-Blue (TB), and Luxol Fast Blue (LFB) were performed. The data were analysed using SPSS version 21. Mean disease scores were significantly lower in P and T1 groups than the PBS group (P = .01). IFN-γ was lower in P and T1 groups than the PBS group. The highest level of IL-4 was observed in T1 group. The total number of neuroglia cells of corpus callosum was similar in all groups, but the density increased in T1 group compared to the PBS group (P = .03). CONCLUSIONS: Dicrocoelium eggs have a great potential to stimulate immunomodulation towards treatment of EAE during the initial phase.
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Dicrocoelium/imunologia , Encefalomielite Autoimune Experimental/terapia , Imunomodulação , Animais , Encefalomielite Autoimune Experimental/imunologia , Encefalomielite Autoimune Experimental/patologia , Encefalomielite Autoimune Experimental/prevenção & controle , Feminino , Interferon gama/imunologia , Interleucina-4/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Óvulo/imunologia , Baço/imunologia , Baço/patologiaRESUMO
The tumor microenvironment consists of noncancerous cells, such as immune cells and fibroblasts, and the proteins produced by these cells as well as the extracellular matrix components in the environment around a tumor. Tumor influences the behavior of the cells present in the surrounding environment, while the cells in the tumor microenvironment modulate the evolution of the tumor. Little is known about the microenvironment of meningioma, the most common benign intracranial tumor. Here, we review the current knowledge of the tumor microenvironment of meningioma and discusses its importance in meningioma tumorigenesis as well as in the designation of novel therapeutic approaches.
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Neoplasias Meníngeas , Meningioma , Carcinogênese , Fibroblastos , Humanos , Microambiente TumoralRESUMO
The adult brain has a very limited regeneration capacity and there is no effective treatment currently available for brain injury. Neuroprotective drugs aim to reduce the intensity of cell degeneration but do not trigger tissue regeneration. Cell replacement therapy is a novel strategy to overcome brain injury-induced disability. To enhance cell viability and neuronal differentiation, developing bioactive scaffolds combined with stem cells for transplantation is a crucial approach in brain tissue engineering. Cell interactions with the extracellular matrix (ECM) play a vital role in neuronal cell survival, neurite outgrowth, attachment, migration, differentiation, and proliferation. Thus, appropriate cell-ECM interactions are essential when designing and modifying scaffolds for application in neural tissue engineering. To improve cell-ECM interactions, scaffolds can be modified with bioactive peptides. Here, we discuss the characteristic features of laminin-derived Ile-Lys-Val-Ala-Val (IKVAV) sequence as a bio-functional motif in scaffolds and the behavior of stem cells in scaffolds conjugated with the IKVAV peptide. The incorporation of this bioactive peptide in nanofiber scaffolds markedly improves stem cell behavior and may be a potential method for cell replacement therapy in traumatic brain injury.
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Lesões Encefálicas Traumáticas/tratamento farmacológico , Laminina/química , Fragmentos de Peptídeos/uso terapêutico , Engenharia Tecidual/métodos , Animais , Terapia Baseada em Transplante de Células e Tecidos , Humanos , Laminina/uso terapêutico , Células-Tronco Neurais/metabolismoRESUMO
Neurodegenerative diseases that include Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), Huntington's disease (HD), and multiple sclerosis (MS) that arise due to numerous causes like protein accumulation and autoimmunity characterized by neurologic depletion which lead to incapacity in normal physiological function such as thinking and movement in these patients. Glial cells perform an important role in protective neuronal function; in the case of neuroinflammation, glial cell dysfunction can promote the development of neurodegenerative diseases. miRNA that participates in gene regulation and plays a vital role in many biological processes in the body; in the central nervous system (CNS), it can play an essential part in neural maturation and differentiation. In neurodegenerative diseases, miRNA dysregulation occurs, enhancing the development of these diseases. In this review, we discuss neurodegenerative disease (Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS)) and how miRNA is preserved as a diagnostic biomarker or therapeutic agent in these disorders. Finally, we highlight miRNA as therapy.
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Biomarcadores , MicroRNAs , Doenças Neurodegenerativas , Humanos , MicroRNAs/genética , Doenças Neurodegenerativas/diagnóstico , Doenças Neurodegenerativas/genética , Doenças Neurodegenerativas/terapia , Biomarcadores/metabolismo , Animais , PrognósticoRESUMO
Despite enormous efforts, no effective medication has been found to significantly halt or even slow the progression of neurological diseases, such as acquired (e.g., traumatic brain injury, spinal cord injury, etc.) and chronic (e.g., Parkinson's disease, Alzheimer's disease, etc.) central nervous system disorders. So, researchers are looking for alternative therapeutic modalities to manage the disease's symptoms and stop it from worsening. Concerning disease-modifying capabilities, stem cell therapy has emerged as an expanding domain. Among different types of stem cells, human endometrial regenerative cells have excellent regenerative properties, making them suitable for regenerative medicine. They have the potential for self-renewal and differentiation into three types of stem cells: epithelial stem cells, endothelial side population stem cells, and mesenchymal stem cells (MSCs). ERCs can be isolated from endometrial biopsy and menstrual blood samples. However, there is no comprehensive evidence on the effects of ERCs on neurological disorders. Hence, we initially explore the traits of these specific stem cells in this analysis, followed by an emphasis on their therapeutic potential in treating neurological disorders.
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BACKGROUND AND OBJECTIVES: Emerging research suggests that hyperammonemia may enhance the probability of hepatic encephalopathy (HE), a condition associated with elevated levels of circulating ammonia in patients with cirrhosis. However, some studies indicate that blood ammonia levels may not consistently correlate with the severity of HE, highlighting the complex pathophysiology of this condition. METHODS: A systematic review and meta-analysis through PubMed, Scopus, Embase, Web of Science, and Virtual Health Library were conducted to address this complexity, analyzing and comparing published data on various laboratory parameters, including circulating ammonia, blood creatinine, albumin, sodium, and inflammation markers in cirrhotic patients, both with and without HE. RESULTS: This comprehensive review, which included 81 studies from five reputable databases until June 2024, revealed a significant increase in circulating ammonia levels in cirrhotic patients with HE, particularly those with overt HE. Notably, significant alterations were observed in the circulating creatinine, albumin, sodium, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNFα) in HE patients. CONCLUSIONS: These findings suggest an association between ammonia and HE and underscore the importance of considering other blood parameters such as creatinine, albumin, sodium, and pro-inflammatory cytokines when devising new treatment strategies for HE.