RESUMO
Clearance of accumulated protein aggregates is one of the functions of autophagy. Recently, a clearer understanding of non-coding RNAs (ncRNAs) functions documented that ncRNAs have important roles in several biological processes associated with the development and progression of neurodegenerative disorders. Subtypes of ncRNA, including microRNA (miRNA), long noncoding RNA (lncRNA), and circular RNA (circRNA), are commonly dysregulated in neurodegenerative disorders such as Alzheimer and Parkinson diseases. Dysregulation of these non-coding RNAs has been associated with inhibition or stimulation of autophagy. Decreased miR-124 led to decreased/increased autophagy in experimental model of Alzheimer and Parkinson diseases. Increased BACE1-AS showed enhanced autophagy in Alzheimer disease by targeting miR-214-3p, Beclin-1, LC3-I/LC3-II, p62, and ATG5. A significant increase in NEAT1led to stimulated autophagy in experimental model of PD by targeting PINK1, LC3-I, LC3-II, p62 and miR-374c-5p. In addition, increased BDNF-AS and SNHG1 decreased autophagy in MPTP-induced PD by targeting miR-125b-5p and miR-221/222, respectively. The upregulation of circNF1-419 and circSAMD4A resulted in an increased autophagy by regulating Dynamin-1 and miR-29c 3p, respectively. A detailed discussion of miRNAs, circRNAs, and lncRNAs in relation to their autophagy-related signaling pathways is presented in this study.
Assuntos
Doença de Alzheimer , MicroRNAs , Doenças Neurodegenerativas , Doença de Parkinson , RNA Longo não Codificante , Humanos , Doença de Parkinson/genética , Doença de Parkinson/metabolismo , Secretases da Proteína Precursora do Amiloide , Doença de Alzheimer/genética , Ácido Aspártico Endopeptidases , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Autofagia/genéticaRESUMO
Neuropsychiatric and neurological disorders pose a significant global health burden, highlighting the need for innovative therapeutic approaches. Fingolimod (FTY720), a common drug to treat multiple sclerosis, has shown promising efficacy against various neuropsychiatric and neurological disorders. Fingolimod exerts its neuroprotective effects by targeting multiple cellular and molecular processes, such as apoptosis, oxidative stress, neuroinflammation, and autophagy. By modulating Sphingosine-1-Phosphate Receptor activity, a key regulator of immune cell trafficking and neuronal function, it also affects synaptic activity and strengthens memory formation. In the hippocampus, fingolimod decreases glutamate levels and increases GABA levels, suggesting a potential role in modulating synaptic transmission and neuronal excitability. Taken together, fingolimod has emerged as a promising neuroprotective agent for neuropsychiatric and neurological disorders. Its broad spectrum of cellular and molecular effects, including the modulation of apoptosis, oxidative stress, neuroinflammation, autophagy, and synaptic plasticity, provides a comprehensive therapeutic approach for these debilitating conditions. Further research is warranted to fully elucidate the mechanisms of action of fingolimod and optimize its use in the treatment of neuropsychiatric and neurological disorders.
Assuntos
Cloridrato de Fingolimode , Doenças do Sistema Nervoso , Fármacos Neuroprotetores , Cloridrato de Fingolimode/uso terapêutico , Cloridrato de Fingolimode/farmacologia , Humanos , Animais , Doenças do Sistema Nervoso/tratamento farmacológico , Doenças do Sistema Nervoso/metabolismo , Fármacos Neuroprotetores/uso terapêutico , Fármacos Neuroprotetores/farmacologia , Cognição/efeitos dos fármacos , Cognição/fisiologia , Transtornos Mentais/tratamento farmacológico , Transtornos Mentais/metabolismo , Moduladores do Receptor de Esfingosina 1 Fosfato/uso terapêutico , Moduladores do Receptor de Esfingosina 1 Fosfato/farmacologia , Estresse Oxidativo/efeitos dos fármacosRESUMO
Neurological disorders are a major group of non-communicable diseases affecting quality of life. Non-Coding RNAs (ncRNAs) have an important role in the etiology of neurological disorders. In studies on the genesis of neurological diseases, aquaporin 4 (AQP4) expression and activity have both been linked to ncRNAs. The upregulation or downregulation of several ncRNAs leads to neurological disorder progression by targeting AQP4. The role of ncRNAs and AQP4 in neurological disorders is discussed in this review.
Assuntos
MicroRNAs , Doenças do Sistema Nervoso , Humanos , Aquaporina 4/genética , Aquaporina 4/metabolismo , Qualidade de Vida , RNA não Traduzido/metabolismo , Doenças do Sistema Nervoso/genética , Regulação para BaixoRESUMO
Gastrointestinal cancer is the most fatal cancer worldwide. The etiology of gastrointestinal cancer has yet to be fully characterized. Alcohol consumption, obesity, tobacco, Helicobacter pylori and gastrointestinal disorders, including gastroesophageal reflux disease, gastric ulcer, colon polyps and non-alcoholic fatty liver disease are among the several risks factors for gastrointestinal cancers. Phycocyanin which is abundant in Spirulina. Phycocyanin, a member of phycobiliprotein family with intense blue color, is an anti-diabetic, neuroprotective, anti-oxidative, anti-inflammatory, and anticancer compound. Evidence exists supporting that phycocyanin has antitumor effects, exerting its pharmacological effects by targeting a variety of cellular and molecular processes, i.e., apoptosis, cell-cycle arrest, migration and Wnt/ß-catenin signaling. Phycocyanin has also been applied in treatment of several gastrointestinal disorders such as, gastric ulcer, ulcerative colitis and fatty liver that is known as a risk factor for progression to cancer. Herein, we summarize various cellular and molecular pathways that are affected by phycocyanin, its efficacy upon combined drug treatment, and the potential for nanotechnology in its gastrointestinal cancer therapy.
Assuntos
Neoplasias Gastrointestinais , Ficocianina , Humanos , Ficocianina/farmacologia , Ficocianina/uso terapêutico , Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias Gastrointestinais/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Gastroenteropatias/tratamento farmacológico , Gastroenteropatias/metabolismoRESUMO
Chimeric antigen receptor (CAR) NK and T cell therapy are promising immunotherapeutic approaches for the treatment of cancer. However, the efficacy of CAR NK/T cell therapy is often hindered by various factors, including the phenomenon of trogocytosis, which involves the bidirectional exchange of membrane fragments between cells. In this review, we explore the role of trogocytosis in CAR NK/T cell therapy and highlight potential strategies for its modulation to improve therapeutic efficacy. We provide an in-depth analysis of trogocytosis as it relates to the fate and function of NK and T cells, focusing on its effects on cell activation, cytotoxicity, and antigen presentation. We discuss how trogocytosis can mediate transient antigen loss on cancer cells, thereby negatively affecting the effector function of CAR NK/T cells. Additionally, we address the phenomenon of fratricide and trogocytosis-associated exhaustion, which can limit the persistence and effectiveness of CAR-expressing cells. Furthermore, we explore how trogocytosis can impact CAR NK/T cell functionality, including the acquisition of target molecules and the modulation of signaling pathways. To overcome the negative effects of trogocytosis on cellular immunotherapy, we propose innovative approaches to modulate trogocytosis and augment CAR NK/T cell therapy. These strategies encompass targeting trogocytosis-related molecules, engineering CAR NK/T cells to resist trogocytosis-induced exhaustion and leveraging trogocytosis to enhance the function of CAR-expressing cells. By overcoming the limitations imposed by trogocytosis, it may be possible to unleash the full potential of CAR NK/T therapy against cancer. The knowledge and strategies presented in this review will guide future research and development, leading to improved therapeutic outcomes in the field of immunotherapy.
Assuntos
Neoplasias , Receptores de Antígenos Quiméricos , Humanos , Células Matadoras Naturais , Trogocitose , Imunoterapia Adotiva , Linfócitos T , Receptores de Antígenos Quiméricos/metabolismo , Neoplasias/metabolismo , Terapia Baseada em Transplante de Células e TecidosRESUMO
The current study aimed to determine the effects of spirulina intake on cognitive function and metabolic status among patients with Alzheimer's disease (AD). This randomized, double-blind, controlled clinical trial was done among 60 subjects with AD. Patients were randomly assigned to receive either 500 mg/day spirulina or a placebo (each n = 30) twice a day for 12 weeks. Mini-mental state examination score (MMSE) was recorded in all patients before and after intervention. Blood samples were obtained at baseline and after 12 weeks' intervention to determine metabolic markers. Compared with placebo, spirulina intake resulted in a significant improvement in MMSE score (spirulina group: +0.30 ± 0.99 vs. Placebo group: -0.38 ± 1.06, respectively, p = 0.01). In addition, spirulina intake decreased high-sensitivity C-reactive protein (hs-CRP) (spirulina group: -0.17 ± 0.29 vs. Placebo group: +0.05 ± 0.27 mg/L, p = 0.006), fasting glucose (spirulina group: -4.56 ± 7.93 vs. Placebo group: +0.80 ± 2.95 mg/dL, p = 0.002), insulin (spirulina group: -0.37 ± 0.62 vs. Placebo group: +0.12 ± 0.40 µIU/mL, p = 0.001) and insulin resistance (spirulina group: -0.08 ± 0.13 vs. Placebo group: 0.03 ± 0.08, p = 0.001), and increased insulin sensitivity (spirulina group: +0.003 ± 0.005 vs. Placebo group: -0.001 ± 0.003, p = 0.003) compared with the placebo. Overall, our study showed that spirulina intake for 12 weeks in patients with AD improved cognitive function, glucose homeostasis parameters, and hs-CRP levels.
Assuntos
Doença de Alzheimer , Resistência à Insulina , Spirulina , Humanos , Suplementos Nutricionais , Proteína C-Reativa/metabolismo , Estresse Oxidativo , Doença de Alzheimer/tratamento farmacológico , Insulina , Método Duplo-Cego , GlicemiaRESUMO
Parkinson's disease (PD) is a progressive neurological disorder characterized by motor and non-motor features. Although some progress has been made in conventional PD treatments, these breakthroughs have yet to show high efficacy in treating this neurodegenerative disease. Probiotics are live microorganisms that confer health benefits on the host when administered in adequate amounts. Probiotics have putative anticancer, antioxidative, anti-inflammatory, and neuroprotective effects. Multiple lines of evidence show that probiotics control and improve several motor and non-motor symptoms in patients and experimental animal models of PD. Probiotic supplementation mediates these pharmacological effects by targeting a variety of cellular and molecular processes, i.e., oxidative stress, inflammatory and anti-inflammatory pathways, as well as apoptosis. Herein, we summarize the effects of probiotics on motor and non-motor symptoms as well as various cellular and molecular pathways in PD.
Assuntos
Doenças Neurodegenerativas , Fármacos Neuroprotetores , Doença de Parkinson , Probióticos , Animais , Anti-Inflamatórios/uso terapêutico , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Probióticos/uso terapêuticoRESUMO
Traumatic brain injury (TBI) is known as an acute degenerative pathology of the central nervous system, and has been shown to increase brain aquaporin 4 (AQP4) expression. Various molecular mechanisms affect AQP4 expression, including neuronal high mobility group box 1, forkhead box O3a, vascular endothelial growth factor, hypoxia-inducible factor-1 α (HIF-1 α) sirtuin 2, NF-κB, Malat1, nerve growth factor and Angiotensin II receptor type 1. In addition, inhibition of AQP4 with FK-506, MK-801 (indirectly by targeting N-methyl-D-aspartate receptor), inactivation of adenosine A2A receptor, levetiracetam, adjudin, progesterone, estrogen, V1aR inhibitor, hypertonic saline, erythropoietin, poloxamer 188, brilliant blue G, HIF-1alpha inhibitor, normobaric oxygen therapy, astaxanthin, epigallocatechin-3-gallate, sesamin, thaliporphine, magnesium, prebiotic fiber, resveratrol and omega-3, as well as AQP4 gene silencing lead to reduced edema upon TBI. This review summarizes current knowledge and evidence on the relationship between AQP4 and TBI, and the potential mechanisms involved.
Assuntos
Edema Encefálico , Lesões Encefálicas Traumáticas , Animais , Aquaporina 4/metabolismo , Edema Encefálico/metabolismo , Lesões Encefálicas Traumáticas/tratamento farmacológico , Lesões Encefálicas Traumáticas/metabolismo , Ratos , Ratos Sprague-Dawley , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Primary brain tumors are a heterogeneous group of tumors that arise from cells intrinsic to the central nervous system (CNS). Aquaporin-4 (AQP4) has been implicated in the pathogenesis of brain tumors. Previous reports have documented a relationship between AQP4 and several molecular pathways associated with the etiology of brain tumors, such as apoptosis, invasion and cell migration. AQP4 affects apoptosis via cytochrome C, Bad and Bcl-2, as well as invasion and migration via IDO1/TDO-Kyn-AhR axis, lncRNA LINC00461, miR-216a, miRNA-320a and MMPs. In addition, inhibition of AQP4 mitigates the progression of brain tumors. This review summarizes current knowledge and evidence regarding the relationship between AQP4 and brain tumors, and the mechanisms involved.
Assuntos
Aquaporina 4 , Neoplasias Encefálicas , Glioma , Humanos , Aquaporina 4/genética , Aquaporina 4/metabolismo , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Glioma/genéticaRESUMO
Glioma is known as one of the most common primary intracranial tumors accounting for four-fifths of malignant brain tumors. There are several biological pathways that play a synergistic, pathophysiological role in glioma, including apoptosis, autophagy, oxidative stress, and cell cycle arrest. According to previous rese arches, the drugs used in the treatment of glioma have been associated with significant limitations. Therefore, improved and/or new therapeutic platforms are required. In this regard, multiple flavonoids and alkaloids have been extensively studied in the treatment of glioma. Berberine is a protoberberine alkaloid with wide range of pharmacological activities, applicable to various pathological conditions. Few studies have reported beneficial roles of berberine in glioma. Berberine exerts its pharmacological functions in glioma by controlling different molecular and cellular pathways. We reviewed the existing knowledge supporting the use of berberine in the treatment of glioma and its effects on molecular and cellular mechanisms.
Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Berberina/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Glioma/tratamento farmacológico , Animais , Antineoplásicos Fitogênicos/farmacologia , Autofagia/efeitos dos fármacos , Autofagia/fisiologia , Berberina/farmacologia , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/radioterapia , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/fisiologia , Quimiorradioterapia/métodos , Glioma/patologia , Glioma/radioterapia , HumanosRESUMO
Parkinson's disease (PD) is an age-associated, progressive, and common neurodegenerative disorder. It is characterized by dopaminergic neuron degeneration in the substantia nigra pars compacta. The involvement of oxidative stress, inflammation, and dysbiosis in PD has been confirmed and probiotics also have the ability to regulate the mentioned mechanisms. Here, we assessed probiotics supplementation effects on experimental model of PD. Thirty Male Wistar rats were divided into three groups for a 14-day treatment. It was shown that a mixture of probiotics containing Lactobacillus acidophilus, Bifidobacterium bifidum, Lactobacillus reuteri, and Lactobacillus fermentum could improve rotational behavior, cognitive function, lipid peroxidation, and neuronal damage in the group received probiotic supplementation compared to the other groups (P < 0001, P < .001, and P = .026, respectively). Taken together, these findings revealed that probiotics supplementation could be an appropriate complementary treatment for PD.
Assuntos
Bifidobacterium bifidum/química , Lactobacillus/química , Fármacos Neuroprotetores/farmacologia , Doença de Parkinson/tratamento farmacológico , Probióticos/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Cognição/efeitos dos fármacos , Suplementos Nutricionais , Modelos Animais de Doenças , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Neurônios/efeitos dos fármacos , Neurônios/patologia , Fármacos Neuroprotetores/administração & dosagem , Oxidopamina , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Probióticos/administração & dosagem , Ratos , Ratos WistarRESUMO
Glioma is the oneof the most prevalent primarybrain tumors. There is a variety of oxidative stresses, inflammatory pathways, apoptosis signaling, and Na+ /H + exchangers (NHEs) involved in the pathophysiology of glioma. Previous studies have indicated a relationship between NHEs and some molecular pathways in glioma. NHEs, including NHE1, NHE5, and NHE9 affect apoptosis, tumor-associated macrophage inflammatory pathways, matrix metalloproteinases, cancer-cell growth, invasion, and migration of glioma. Also, inhibition of NHEs contributes to increased survival in animal models of glioma. Limited studies, however, have assessed the relationship between NHEs and molecular pathways in glioma. This review summarizes current knowledge and evidence regarding the relationship between NHEs and glioma, and the mechanisms involved.
Assuntos
Antineoplásicos/farmacologia , Glioma/tratamento farmacológico , Trocadores de Sódio-Hidrogênio/antagonistas & inibidores , Trocadores de Sódio-Hidrogênio/metabolismo , Proliferação de Células/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/fisiologia , Glioma/metabolismo , Humanos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Trocadores de Sódio-Hidrogênio/genéticaRESUMO
Parkinson disease (PD) is a chronic and neurodegenerative disease with motor and nonmotor symptoms. Multiple pathways are involved in the pathophysiology of PD, including apoptosis, autophagy, oxidative stress, inflammation, α-synuclein aggregation, and changes in the neurotransmitters. Preclinical and clinical studies have shown that melatonin supplementation is an appropriate therapy for PD. Administration of melatonin leads to inhibition of some pathways related to apoptosis, autophagy, oxidative stress, inflammation, α-synuclein aggregation, and dopamine loss in PD. In addition, melatonin improves some nonmotor symptom in patients with PD. Limited studies, however, have evaluated the role of melatonin on molecular mechanisms and clinical symptoms in PD. This review summarizes what is known regarding the impact of melatonin on PD in preclinical and clinical studies.
Assuntos
Melatonina/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Modelos Animais de Doenças , Humanos , Melatonina/farmacologia , Estresse Oxidativo/efeitos dos fármacosRESUMO
Glioma is the most common primary brain tumor, and is a major health problem throughout the world. Today, researchers have discovered many risk factors that are associated with the initiation and progression of gliomas. Studies have shown that PIWI-interacting RNAs (piRNAs) and PIWI proteins are involved in tumorigenesis by epigenetic mechanisms. Hence, it seems that piRNAs and PIWI proteins may be potential prognostic, diagnostic or therapeutic biomarkers in the treatment of glioma. Previous studies have demonstrated a relationship between piRNAs and PIWI proteins and some of the molecular and cellular pathways in glioma. Here, we summarize recent evidence and evaluate the molecular mechanisms by which piRNAs and PIWI proteins are involved in glioma. Video abstract.
Assuntos
Proteínas Argonautas/metabolismo , Biomarcadores Tumorais/metabolismo , Glioma/metabolismo , RNA Interferente Pequeno/metabolismo , Animais , Epigênese Genética , Glioma/genética , Glioma/patologia , Humanos , Modelos BiológicosRESUMO
Aims: This systematic review and meta-analysis of randomized controlled trials (RCTs) was performed to determine the effect of quercetin administration on lipid profiles and inflammatory markers among patients with metabolic syndrome (MetS) and related disorders.Methods: We searched systematically online databases including Cochrane Library, EMBASE, MEDLINE, and Web of Science to identify the relevant RCTs until November 2018. Q-test and I2 statistics were applied to assess heterogeneity among included studies. Data were combined using fixed- or random-effects model and presented as standardized mean difference (SMD) with 95% confidence interval (CI).Results: Out of 591 citations, 16 RCTs were included in the meta-analysis. The pooled findings showed that quercetin consumption significantly decreased total-cholesterol (SMD = -0.98; 95% CI, -1.48, -0.49; p < 0.001; I2: 94.0), LDL-cholesterol (SMD = -0.88; 95% CI, -1.35, -0.41; p < 0.001; I2: 92.7) and C-reactive protein (CRP) levels (-0.64; 95% CI, -1.03, -0.25; p = 0.001; I2: 90.2). While, quercetin supplementation did not significantly affect triglycerides (TG) (SMD = -0.32; 95% CI, -0.68, 0.04; p = 0.08; I2: 84.8), HDL-cholesterol (SMD = 0.20; 95% CI, -0.20, 0.24; p = 0.84; I2: 70.6), interleukin 6 (IL-6) (SMD = -0.69; 95% CI, -1.69, 0.31; p = 0.17; I2: 94.5) and tumor necrosis factor-alpha (TNF-α) levels (SMD = -0.06; 95% CI, -0.25, 0.14; p = 0.58; I2: 35.6)Conclusions: In summary, the current meta-analysis demonstrated that quercetin supplementation significantly reduced total-cholesterol, LDL-cholesterol, and CRP levels, yet did not affect triglycerides, HDL-cholesterol, IL-6 and TNF-α among patients with MetS and related disorders.
Assuntos
Suplementos Nutricionais , Lipídeos/sangue , Síndrome Metabólica/terapia , Quercetina/administração & dosagem , Humanos , Inflamação , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
This systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to summarize the effect of resveratrol intake on weight loss. We searched the following databases until July 2018: MEDLINE, EMBASE, Web of Science and Cochrane Central Register of Controlled Trials. Data were pooled using the inverse variance method and expressed as standardized mean difference (SMD) with 95% confidence intervals (95% CI). Out of 831 reports, 36 RCTs were eligible for including to our meta-analysis. The pooled results, using random-effects model showed that resveratrol supplementation significantly decreased body weight (SMD = -0.17; 95% CI, -0.33, -0.01; P = 0.03; I2: 62.6), body mass index (BMI) (SMD = -0.20; 95% CI, -0.35, -0.05; P = 0.01; I2: 60.6), fat mass (SMD = -0.32; 95% CI, -0.62, -0.03; P = 0.03; I2: 77.9) and waist circumference (WC) (SMD = -0.42; 95% CI, -0.68, -0.16; P = 0.001; I2: 75.2), and significantly increased lean mass (SMD = 1.21; 95% CI, 0.75, 1.67; P < 0.001; I2: 87.6). We found no significant effect of resveratrol administration on leptin (SMD = -0.20; 95% CI, -0.68, 0.27; P = 0.40; I2: 85.3) and adiponectin levels (SMD = 0.08; 95% CI, -0.39, 0.55; P = 0.74; I2: 91.0). Resveratrol supplementation significantly decreased body weight in obese patients (SMD -0.43; 95% CI, -0.60, -0.26) compared with other diseases (SMD 0.02; 95% CI, -0.29, 0.33), and type 2 diabetes mellitus (SMD -0.17; 95% CI, -0.37, 0.02). Overall, the current meta-analysis demonstrated that resveratrol intake significantly reduced weight, BMI, WC and fat mass, and significantly increased lean mass, but did not affect leptin and adiponectin levels.
Assuntos
Resveratrol/farmacologia , Redução de Peso/efeitos dos fármacos , Adiponectina/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Suplementos Nutricionais , Humanos , Leptina/metabolismo , Obesidade/metabolismo , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: There are current trials investigating the effect of resveratrol supplementation on lipid profiles and liver enzymes among patients with metabolic syndrome (MetS) and related disorders; however, their findings are controversial. This systematic review and meta-analysis were aimed to determine the effects of resveratrol supplementation on lipid profiles and liver enzymes among patients with MetS and related disorders. METHODS: We performed a comprehensive search of the following online databases up to November 2018: Cochrane Library, PubMed, Embase, and Web of Science. The relevant articles were assessed for quality of studies using the Cochrane risk of bias tool. RESULTS: Out of 2459 citations, 31 articles were appropriate for including to the current meta-analysis. The pooled results indicated that resveratrol use significantly decreased total cholesterol [weighted mean difference (WMD) = - 7.65 mg/dL; 95% CI, - 12.93, - 2.37; P < 0.01; I2: 83.4%] and increased gamma-glutamyl transferase (GGT) concentrations (WMD = 1.76 U/l; 95% CI, 0.58, 2.94; P < 0.01; I2: 20.1%). We found no significant effect of resveratrol supplementation on triglycerides (WMD = - 5.84 mg/dL; 95% CI, - 12.68, 1.00; P = 0.09; I2: 66.8%), LDL- (WMD = -2.90 mg/dL; 95% CI, - 10.88, 5.09; P = 0.47; I2: 96.0%), HDL-cholesterol (WMD = 0.49 mg/dL; 95% CI, - 0.80, 1.78; P = 0.45; I2: 74.0%), alanine aminotransferase (ALT) (WMD = -0.14 U/l; 95% CI, - 3.69, 3.41; P = 0.93; I2: 79.6%), and aspartate aminotransferase (AST) (WMD = -0.34 U/l; 95% CI, - 2.94, 2.27; P = 0.80; I2: 88.0%) concentrations. CONCLUSIONS: This meta-analysis demonstrated that resveratrol supplementation among patients with MetS and related disorders significantly reduced total cholesterol and increased GGT concentrations, but did not affect triglycerides, LDL-, HDL-cholesterol, ALT, and AST concentrations. This data suggests that resveratrol may have a potential cardio-protective effect in patients with MetS and related disorders.
Assuntos
Síndrome Metabólica/tratamento farmacológico , Síndrome Metabólica/metabolismo , Resveratrol/uso terapêutico , Animais , Colesterol/sangue , Humanos , Síndrome Metabólica/sangue , Ensaios Clínicos Controlados Aleatórios como Assunto , Triglicerídeos/sangueRESUMO
Parkinson's disease (PD) is one of the most prevalent neurodegenerative diseases which occur in aged people worldwide. Given that a sequence of cellular and molecular mechanisms, including oxidative stresses, apoptosis, inflammatory pathways, microglia, astrocyte activation, and aquaporin 4 (AQP4) are associated with initiation and the progression of PD. AQP4 may affect various pathways (i.e., α-synuclein, inflammatory pathways, and microglia and astrocyte activation). Few reports have evaluated the relationship between AQP4 and PD-related cellular and molecular pathways. Here, for the first time, we highlighted the relationship between AQP4 and molecular mechanisms involved in PD pathogenesis.
Assuntos
Aquaporina 4/metabolismo , Doença de Parkinson/metabolismo , Animais , Apoptose/fisiologia , Astrócitos/metabolismo , Humanos , Inflamação/metabolismo , Microglia/metabolismo , Estresse Oxidativo/fisiologiaRESUMO
Dysregulation of neuronal Ca2+ and oxidative stress plays an important role in the activation of cysteine proteases including calpains and caspases that contribute to neuronal death. In neurodegenerative diseases, traumatic brain injury, stroke, and neuropathic pain calpain activities are markedly increased. Melatonin is a beneficial supplement in the treatment of central nervous system (CNS) disorders. Melatonin is a potent antioxidant and works as a free-radical scavenger to regulate a large number of molecular pathways, including oxidative stress, inflammation, apoptosis, and cell death under different pathological conditions. However, limited studies have evaluated the inhibitory effect of melatonin on calpains. This review summarizes the current knowledge related to the effects of melatonin on calpains in some of the common CNS disorders.
Assuntos
Calpaína/antagonistas & inibidores , Doenças do Sistema Nervoso Central/tratamento farmacológico , Sistema Nervoso Central/efeitos dos fármacos , Inibidores de Cisteína Proteinase/uso terapêutico , Melatonina/uso terapêutico , Animais , Calpaína/metabolismo , Sistema Nervoso Central/enzimologia , Sistema Nervoso Central/patologia , Sistema Nervoso Central/fisiopatologia , Doenças do Sistema Nervoso Central/enzimologia , Doenças do Sistema Nervoso Central/patologia , Doenças do Sistema Nervoso Central/fisiopatologia , Humanos , Transdução de SinaisRESUMO
Pancreatic cancer has a high mortality rate due to the absence of early symptoms and subsequent late diagnosis; additionally, pancreatic cancer has a high resistance to radio- and chemotherapy. Multiple inflammatory pathways are involved in the pathophysiology of pancreatic cancer. Melatonin an indoleamine produced in the pineal gland mediated and receptor-independent action is the pancreas and other where has both receptors. Melatonin is a potent antioxidant and tissue protector against inflammation and oxidative stress. In vivo and in vitro studies have shown that melatonin supplementation is an appropriate therapeutic approach for pancreatic cancer. Melatonin may be an effective apoptosis inducer in cancer cells through regulation of a large number of molecular pathways including oxidative stress, heat shock proteins, and vascular endothelial growth factor. Limited clinical studies, however, have evaluated the role of melatonin in pancreatic cancer. This review summarizes what is known regarding the effects of melatonin on pancreatic cancer and the mechanisms involved.