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Membrane trafficking is a physiological process encompassing different pathways involved in transporting cellular products across cell membranes to specific cell locations via encapsulated vesicles. This process is required for cells to mature and function properly, allowing them to adapt to their surroundings. The retromer complex is a complex composed of nexin proteins and peptides that play a vital role in the endosomal pathway of membrane trafficking. In humans, any interference in normal membrane trafficking or retromer complex can cause profound changes such as those seen in neurodegenerative disorders such as Alzheimer's and Parkinson's. Several studies have explored the potential causative mechanisms in developing both disease processes; however, the role of retromer trafficking in their pathogenesis is becoming increasingly significant with promising therapeutic applications. This manuscript describes the processes involved in membrane transport and the roles of the retromer in the onset and progression of Alzheimer's and Parkinson's. Moreover, we will also explore how these aberrant mechanisms may serve as possible avenues for treatment development in both diseases and the prospect of its future application.
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Doença de Alzheimer , Doença de Parkinson , Humanos , Membrana Celular , Transporte Biológico , Proteínas Associadas aos MicrotúbulosRESUMO
Aquaporins (AQPs) are ubiquitous channel proteins that play a critical role in the homeostasis of the cellular environment by allowing the transit of water, chemicals, and ions. They can be found in many different types of cells and organs, including the lungs, eyes, brain, glands, and blood vessels. By controlling the osmotic water flux in processes like cell growth, energy metabolism, migration, adhesion, and proliferation, AQPs are capable of exerting their regulatory influence over a wide range of cellular processes. Tumour cells of varying sources express AQPs significantly, especially in malignant tumours with a high propensity for metastasis. New insights into the roles of AQPs in cell migration and proliferation reinforce the notion that AQPs are crucial players in tumour biology. AQPs have recently been shown to be a powerful tool in the fight against pathogenic antibodies and metastatic cell migration, despite the fact that the molecular processes of aquaporins in pathology are not entirely established. In this review, we shall discuss the several ways in which AQPs are expressed in the body, the unique roles they play in tumorigenesis, and the novel therapeutic approaches that could be adopted to treat carcinoma.
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Aquaporinas , Neoplasias , Humanos , Neoplasias/patologia , Carcinogênese , Transformação Celular Neoplásica , Água/metabolismo , Aquaporinas/química , Aquaporinas/metabolismoRESUMO
Parkinson's disease is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms, including hallucinations. The use of antipsychotic medications is a common strategy to manage hallucinations associated with Parkinson's disease psychosis (PDP). However, careful consideration is necessary when selecting the most appropriate drug due to the potential risks associated with the available treatment options. Atypical antipsychotics (AAPs), such as Pimavanserin and Clozapine, have effectively controlled PDP symptoms. On the contrary, the support for utilizing quetiapine is not as substantial as other antipsychotics because research studies specifically investigating its application are still emerging and relatively recent. The broad mechanisms of action of AAPs, involving dopamine and serotonin receptors, provide improved outcomes and fewer side effects than typical antipsychotics. Conversely, other antipsychotics, including risperidone, olanzapine, aripiprazole, ziprasidone, and lurasidone, have been found to worsen motor symptoms and are generally not recommended for PDP. While AAPs offer favorable benefits, they are associated with specific adverse effects. Extrapyramidal symptoms, somnolence, hypotension, constipation, and cognitive impairment are commonly observed with AAP use. Clozapine, in particular, carries a risk of agranulocytosis, necessitating close monitoring of blood counts. Pimavanserin, a selective serotonin inverse agonist, avoids receptor-related side effects but has been linked to corrected QT (QTc) interval prolongation, while quetiapine has been reported to be associated with an increased risk of mortality. This review aims to analyze the benefits, risks, and mechanisms of action of antipsychotic medications to assist clinicians in making informed decisions and enhance patient care.
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Antipsicóticos , Clozapina , Alucinações , Doença de Parkinson , Piperidinas , Fumarato de Quetiapina , Humanos , Antipsicóticos/administração & dosagem , Antipsicóticos/efeitos adversos , Antipsicóticos/farmacologia , Clozapina/efeitos adversos , Clozapina/administração & dosagem , Clozapina/farmacologia , Alucinações/tratamento farmacológico , Alucinações/etiologia , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/complicações , Piperidinas/efeitos adversos , Piperidinas/farmacologia , Piperidinas/administração & dosagem , Fumarato de Quetiapina/efeitos adversos , Fumarato de Quetiapina/farmacologia , Fumarato de Quetiapina/administração & dosagem , Ureia/análogos & derivados , Ureia/farmacologia , Ureia/efeitos adversosRESUMO
The genus Cornus (Cornaceae) plants are widely distributed in Europe, southwest Asia, North America, and the mountains of Central America, South America, and East Africa. Cornus plants exhibit antimicrobial, antioxidative, antiproliferative, cytotoxic, antidiabetic, anti-inflammatory, neuroprotective and immunomodulatory activities. These plants are exploited to possess various phytoconstituents such as triterpenoids, iridoids, anthocyanins, tannins and flavonoids. Pharmacological research and clinical investigations on various Cornus species have advanced significantly in recent years. Over the past few decades, a significant amount of focus has also been made into developing new delivery systems for Cornus mas and Cornus officinalis. This review focuses on the morphological traits, ethnopharmacology, phytochemistry, pharmacological activities and clinical studies on extracts and active constituents from plants of Cornus genus. The review also highlights recent novel delivery systems for Cornus mas and Cornus officinalis extracts to promote sustained and targeted delivery in diverse disorders. The overwhelming body of research supports the idea that plants from the genus Cornus have therapeutic potential and can be investigated in the future for treatingseveral ailments.
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Cornus , Extratos Vegetais , Humanos , Cornus/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/isolamento & purificação , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/isolamento & purificação , Animais , Sistemas de Liberação de MedicamentosRESUMO
Glioblastoma multiforme (GBM) is the most common form of brain cancer and one of the most aggressive cancers found in humans. Most of the signs and symptoms of GBM can be mild and slowly aggravated, although other symptoms might demonstrate it as an acute ailment. However, the precise mechanisms of the development of GBM remain unknown. Due to the improvement of molecular pathology, current researches have reported that glioma progression is strongly connected with different types of epigenetic phenomena, such as histone modifications, DNA methylation, chromatin remodeling, and aberrant microRNA. Furthermore, the genes and the proteins that control these alterations have become novel targets for treating glioma because of the reversibility of epigenetic modifications. In some cases, gene mutations including P16, TP53, and EGFR, have been observed in GBM. In contrast, monosomies, including removals of chromosome 10, particularly q23 and q25-26, are considered the standard markers for determining the development and aggressiveness of GBM. Recently, amid the epigenetic therapies, histone deacetylase inhibitors (HDACIs) and DNA methyltransferase inhibitors have been used for treating tumors, either single or combined. Specifically, HDACIs are served as a good choice and deliver a novel pathway to treat GBM. In this review, we focus on the epigenetics of GBM and the consequence of its mutations. We also highlight various treatment approaches, namely gene editing, epigenetic drugs, and microRNAs to combat GBM.
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Neoplasias Encefálicas , Glioblastoma , Glioma , MicroRNAs , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Metilação de DNA , Epigênese Genética , Epigenômica , Glioblastoma/tratamento farmacológico , Glioblastoma/genética , Glioma/genética , Humanos , MicroRNAs/genéticaRESUMO
Brain cancer is an aggressive type of cancer with poor prognosis. While the immune system protects against cancer in the early stages, the tumor exploits the healing arm of inflammatory reactions to accelerate its growth and spread. Various immune cells penetrate the developing tumor region, establishing a pro-inflammatory tumor milieu. Additionally, tumor cells may release chemokines and cytokines to attract immune cells and promote cancer growth. Inflammation and its associated mechanisms in the progression of cancer have been extensively studied in the majority of solid tumors, especially brain tumors. However, treatment of the malignant brain cancer is hindered by several obstacles, such as the blood-brain barrier, transportation inside the brain interstitium, inflammatory mediators that promote tumor growth and invasiveness, complications in administering therapies to tumor cells specifically, the highly invasive nature of gliomas, and the resistance to drugs. To resolve these obstacles, nanomedicine could be a potential strategy that has facilitated advancements in diagnosing and treating brain cancer. Due to the numerous benefits provided by their small size and other features, nanoparticles have been a prominent focus of research in the drug-delivery field. The purpose of this article is to discuss the role of inflammatory mediators and signaling pathways in brain cancer as well as the recent advances in understanding the nano-carrier approaches for enhancing drug delivery to the brain in the treatment of brain cancer.
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Neoplasias Encefálicas , Nanomedicina , Humanos , Neoplasias Encefálicas/metabolismo , Sistemas de Liberação de Medicamentos , Inflamação/tratamento farmacológico , Mediadores da Inflamação/uso terapêuticoRESUMO
Recent mounting evidence has revealed extensive genetic heterogeneity within tumors that drive phenotypic variation affecting key cancer pathways, making cancer treatment extremely challenging. Diverse cancer types display resistance to treatment and show patterns of relapse following therapy. Therefore, efforts are required to address tumor heterogeneity by developing a broad-spectrum therapeutic approach that combines targeted therapies. Inflammation has been progressively documented as a vital factor in tumor advancement and has consequences in epigenetic variations that support tumor instigation, encouraging all the tumorigenesis phases. Increased DNA damage, disrupted DNA repair mechanisms, cellular proliferation, apoptosis, angiogenesis, and its incursion are a few pro-cancerous outcomes of chronic inflammation. A clear understanding of the cellular and molecular signaling mechanisms of tumor-endorsing inflammation is necessary for further expansion of anti-cancer therapeutics targeting the crosstalk between tumor development and inflammatory processes. Multiple inflammatory signaling pathways, such as the NF-κB signaling pathway, JAK-STAT signaling pathway, MAPK signaling, PI3K/AKT/mTOR signaling, Wnt signaling cascade, and TGF-ß/Smad signaling, have been found to regulate inflammation, which can be modulated using various factors such as small molecule inhibitors, phytochemicals, recombinant cytokines, and nanoparticles (NPs) in conjugation to phytochemicals to treat cancer. Researchers have identified multiple targets to specifically alter inflammation in cancer therapy to restrict malignant progression and improve the efficacy of cancer therapy. siRNA-and shRNA-loaded NPs have been observed to downregulate STAT3 signaling pathways and have been employed in studies to target tumor malignancies. This review highlights the pathways involved in the interaction between tumor advancement and inflammatory progression, along with the novel approaches of nanotechnology-based drug delivery systems currently used to target inflammatory signaling pathways to combat cancer.
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Nanomedicina , Fosfatidilinositol 3-Quinases , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Compreensão , Recidiva Local de Neoplasia , Transdução de Sinais , Inflamação/tratamento farmacológicoRESUMO
BACKGROUND: Globally, diabetes mellitus is the most common cause of premature mortality after cardiovascular diseases and tobacco chewing. It is a heterogeneous metabolic disorder characterised by the faulty metabolism of carbohydrates, fats and proteins as a result of defects in insulin secretion or resistance. It was estimated that approximately 463 million of the adult population are suffering from diabetes mellitus, which may grow up to 700 million by 2045. Solanum indicum is distributed all over India and all of the tropical and subtropical regions of the world. The different parts of the plant such as the roots, leaves and fruits were used traditionally in the treatment of cough, asthma and rhinitis. However, the hypoglycaemic activity of the plant is not scientifically validated. PURPOSE: The present study aimed to evaluate the antioxidant, antidiabetic and anti-hyperlipidaemic activity of methanolic fruit extract of Solanum indicum (SIE) in streptozotocin (STZ) induced diabetic rats. METHOD: Experimentally, type II diabetes was induced in rats by an i.p. injection of STZ at a dose of 60 mg/kg. The effect of the fruit extract was evaluated at doses of 100 and 200 mg/kg body weight in STZ-induced diabetic rats for 30 days. RESULT: The oral administration of fruit extract caused a significant (p < 0.05) reduction in the blood glucose level with a more prominent effect at 200 mg/kg. The fruit extract showed dose-dependent α-amylase and α-glycosidase inhibitory activity. It reduced the serum cholesterol and triglyceride levels remarkably in diabetic rats compared to normal. The extract showed the reduced activity of endogenous antioxidants, superoxide dismutase, glutathione peroxidase and catalase in the liver of STZ diabetic rats. CONCLUSION: The result confirmed that the fruit extract of Solanum indicum showed a dose-dependent blood glucose lowering effect and significantly reduced elevated blood cholesterol and triglycerides. It prevented oxidative stress associated with type II diabetes in STZ rats.
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Glioblastoma (GB) are aggressive tumors that obstruct normal brain function. While the skull cannot expand in response to cancer growth, the growing pressure in the brain is generally the first sign. It can produce more frequent headaches, unexplained nausea or vomiting, blurred peripheral vision, double vision, a loss of feeling or movement in an arm or leg, and difficulty speaking and concentrating; all depend on the tumor's location. GB can also cause vascular thrombi, damaging endothelial cells and leading to red blood cell leakage. Latest studies have revealed the role of single nucleotide polymorphisms (SNPs) in developing and spreading cancers such as GB and breast cancer. Many discovered SNPs are associated with GB, particularly in great abundance in the promoter region, creating polygenetic vulnerability to glioma. This study aims to compile a list of some of the most frequent and significant SNPs implicated with GB formation and proliferation.
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Neoplasias Encefálicas , Glioblastoma , Glioma , Humanos , Glioblastoma/genética , Glioblastoma/patologia , Células Endoteliais/patologia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Encéfalo/patologiaRESUMO
Frequent consumption of fruits and vegetables in the daily diet may alleviate the risk of developing chronic diseases. Daucus carota L. (carrot), Beta vulgaris L. (beetroot) Phyllanthus emblica L. (amla), and Lycopersicon esculentum M (tomatoes) are traditionally consumed functional foods that contain a high concentration of antioxidants, ascorbic acid, polyphenols, and numerous phytochemicals. This study assessed how three distinct preparation methods affect the phenolic, flavonoid, carotenoid, and ascorbic acid contents, antioxidant level, and cytotoxicity of the combined fruit extract. The fruit samples were taken in the ratio of carrot (6): beetroot (2): tomato (1.5): amla (0.5) and processed into a lyophilized slurry (LS) extract, lyophilized juice (LJ) extract, and hot-air oven-dried (HAO) extract samples. The sample extracts were assessed for their phytoconstituent concentrations and antioxidant and cytotoxic potential. The total phenolic content in LS, LJ, and HAO extracts was 171.20 ± 0.02, 120.73 ± 0.02, and 72.05 ± 0.01 mg gallic acid equivalent/100 g, respectively and the total flavonoid content was 23.635 ± 0.003, 20.754 ± 0.005, and 18.635 ± 0.005 mg quercetin equivalent/100 g, respectively. Similarly, total ascorbic acid content, carotenoids, and antioxidant potential were higher in the LS and LJ extracts than in HAO. Overall, the LS extract had a substantially higher concentration of phytochemicals and antioxidants, as well as higher cytotoxic potential, compared to the LJ and HAO extracts. The LS extract was tested in the MKN-45 human gastric cancer cell line to demonstrate its effective antioxidant potential and cytotoxicity. Hence, lyophilization (freezing) based techniques are more effective than heat-based techniques in preserving the phytoconstituents and their antioxidant and cytotoxic potential.
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Beta vulgaris , Daucus carota , Phyllanthus emblica , Solanum lycopersicum , Neoplasias Gástricas , Humanos , Antioxidantes/análise , Phyllanthus emblica/química , Phyllanthus emblica/metabolismo , Daucus carota/metabolismo , Beta vulgaris/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Extratos Vegetais/farmacologia , Extratos Vegetais/análise , Ácido Ascórbico/análise , Fenóis/farmacologia , Fenóis/análise , Flavonoides/farmacologia , Flavonoides/análise , Carotenoides/farmacologia , Carotenoides/análise , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/análise , Frutas/químicaRESUMO
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Extracellular vehicles (EVs) are nanoscale lipid bilayer vesicles that carry biologically active biomolecule cargos like proteins, lipids, and nucleic acids (DNA, RNA) outside of the cell. Blood (serum/plasma), urine, and bronchoalveolar lavage fluid are all examples of biofluids from which they may be collected. EVs play a vital role in intracellular communication. The molecular signature of EVs largely depends on the parental cell's status. EVs are classified into two groups, (1) exosomes (originated by endogenous route) and (2) microvesicles (originated from the plasma membrane, also known as ectosomes). The quantity and types of EV cargo vary during normal conditions compared to pathological conditions (chronic inflammatory lung diseases or lung cancer). Consequently, EVs contain novel biomarkers that differ based on the cell type of origin and during lung diseases. Small RNAs (e.g., microRNAs) are transported by EVs, which is one of the most rapidly evolving research areas in the field of EVs biology. EV-mediated cargos transport small RNAs that can result in reprograming the target/recipient cells. Multiple chronic inflammatory lung illnesses, such as chronic obstructive pulmonary disease, asthma, pulmonary hypertension, pulmonary fibrosis, cystic fibrosis, acute lung injury, and lung cancer, have been demonstrated to be regulated by EV. In this review, we will consolidate the current knowledge and literature on the novel role of EVs and their small RNAs concerning chronic lung diseases (CLDs). Additionally, we will also provide better insight into the clinical and translational impact of mesenchymal stem cells-derived EVs as novel therapeutic agents in treating CLDs.
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Exossomos , Vesículas Extracelulares , Pneumopatias , Neoplasias Pulmonares , MicroRNAs , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Vesículas Extracelulares/genética , Vesículas Extracelulares/metabolismo , Exossomos/genética , Exossomos/metabolismo , Pneumopatias/genética , Neoplasias Pulmonares/metabolismoRESUMO
Stroke, whether ischemic or haemorrhagic, is one of the main causes of mortality and disability all over the world, which entails huge burdens in both healthcare environments as well as social and economic aspects of life. Therefore, there is a continuous search for novel reliable biomarkers that can enhance the recognition of stroke events in a timely manner and predict the clinical outcomes following a stroke event. Galectins are a group of proteins expressed by many types of cells and tissues including vasculature, certain immune cells, fibroblasts, and gastrointestinal epithelial cells. These proteins vary in their structure and configuration according to their type and have a diversity of functions according to the type of tissue they are expressed in. Among these proteins, a few studies investigated mainly the roles played by galectin-1 (Gal-1) and galectin-3 (Gal-3) in the molecular mechanisms of atherosclerosis and in brain tissue remodeling after a stroke event. In this review, we present an updated overview of the current understanding of Gal-3's functions and implications in stroke occurrence and the response of the brain tissue to stroke events, which may be a key to its utility as a predictor of stroke incidence and clinical prognosis in the future.
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Proteínas Sanguíneas , Galectina 3 , Galectinas , Acidente Vascular Cerebral , Biomarcadores , Proteínas Sanguíneas/análise , Galectinas/análise , Humanos , Incidência , Prognóstico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologiaRESUMO
Microglial cells serve as molecular sensors of the brain that play a role in physiological and pathological conditions. Under normal physiology, microglia are primarily responsible for regulating central nervous system homeostasis through the phagocytic clearance of redundant protein aggregates, apoptotic cells, damaged neurons, and synapses. Furthermore, microglial cells can promote and mitigate amyloid ß phagocytosis and tau phosphorylation. Dysregulation of the microglial programming alters cellular morphology, molecular signaling, and secretory inflammatory molecules that contribute to various neurodegenerative disorders especially Alzheimer's disease (AD). Furthermore, microglia are considered primary sources of inflammatory molecules and can induce or regulate a broad spectrum of cellular responses. Interestingly, in AD, microglia play a double-edged role in disease progression; for instance, the detrimental microglial effects increase in AD while microglial beneficiary mechanisms are jeopardized. Depending on the disease stages, microglial cells are expressed differently, which may open new avenues for AD therapy. However, the disease-related role of microglial cells and their receptors in the AD brain remain unclear. Therefore, this review represents the role of microglial cells and their involvement in AD pathogenesis.
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Doença de Alzheimer , Microglia , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Encéfalo/metabolismo , Humanos , Microglia/metabolismo , FagocitoseRESUMO
Stress has become a dangerous health problem in our life, especially in student education journey. Accordingly, previous methods have been conducted to detect mental stress based on biological and biochemical effects. Moreover, hormones, physiological effects, and skin temperature have been extensively used for stress detection. However, based on the recent literature, biological, biochemical, and physiological-based methods have shown inconsistent findings, which are initiated due to hormones' instability. Therefore, it is crucial to study stress using different mechanisms such as Electroencephalogram (EEG) signals. In this research study, the frontal lobes EEG spectrum analysis is applied to detect mental stress. Initially, we apply a Fast Fourier Transform (FFT) as a feature extraction stage to measure all bands' power density for the frontal lobe. After that, we used two type of classifications such as subject wise and mix (mental stress vs. control) using Support Vector Machine (SVM) and Naive Bayes (NB) machine learning classifiers. Our obtained results of the average subject wise classification showed that the proposed technique has better accuracy (98.21%). Moreover, this technique has low complexity, high accuracy, simple and easy to use, no over fitting, and it could be used as a real-time and continuous monitoring technique for medical applications.
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Eletroencefalografia/métodos , Lobo Frontal/fisiopatologia , Aprendizado de Máquina , Processamento de Sinais Assistido por Computador , Estresse Psicológico/diagnóstico , Estresse Psicológico/fisiopatologia , Adulto , Eletroencefalografia/normas , Feminino , Análise de Fourier , Humanos , Masculino , Sensibilidade e Especificidade , Máquina de Vetores de Suporte , Adulto JovemRESUMO
Citrus limon L. is an ingenious alternative medication and has a broad scope in managing several health conditions as part of natural remedies. Recently, medicinal plants have witnessed incredible consideration worldwide in the field of neuroscience for remedial intervention. The present work has investigated the phytochemical compounds and neuropharmacological potential of the seed extract of Citrus limon as a step to partially validate its formulations as nutraceuticals using an in vivo model. Diverse phytochemical groups such as alkaloids, glycosides, flavonoids, tannins, gums, saponins, steroids were qualitatively identified through colorimetric methods utilizing standard compounds. The neuropharmacological properties were studied in Swiss albino mice with the sleep time induced by thiopental sodium taken as an end-point, in standard hole cross, hole board, and open-field experiments at varying doses of 50 and 100 mg/kg body weight. Phytochemical screening showed that alkaloids, flavonoids, saponins, tannins, steroids, and glycosides are present in the aqueous extract of the seed. The extracts demonstrated a significant reduction in sleep onset and enhanced the sleep duration in a dose-dependent manner in thiopental sodium-induced sleeping time, along with a marked decrease in unconstrained locomotors and explorative properties in both hole cross and open field tests. Moreover, in the hole board study, the extracts minimized the count of head dips observed in the treated mice. The results shown in this study demonstrate that Citrus limon extracts have neuropharmacological properties that can be further examined for their potential role as an adjuvant with conventional medications or nutraceuticals.
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Citrus , Neurotransmissores/farmacologia , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Sementes , Sono/efeitos dos fármacos , Animais , Comportamento Animal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Hipnóticos e Sedativos/farmacologia , Locomoção/efeitos dos fármacos , Modelos Animais , Tiopental/farmacologia , Fatores de TempoRESUMO
Computational approach to study of neuronal impairment is rapidly evolving, as experiments and intuition alone could not explain the complexity of brain system. The increase in an overwhelming amount of new data from both theory and computational modeling necessitate the development of databases and tools for analysis, visualization, and interpretation of neuroscience data. To ensure the sustainability of this development, consistent update and training of young professionals are imperative. For this purpose, relevant articles, chapters, and modules are essential to keep abreast of developments. Therefore, this article seeks to outline the biological databases and analytical tools along with their applications. It's envisaged that knowledge along this line would be a "training recipe" for young talents and guide for professionals and researchers in neuroscience.
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Biologia Computacional , Bases de Dados Factuais , Doenças do Sistema Nervoso , HumanosRESUMO
Advancements in medicine have increased the longevity of humans, resulting in a higher incidence of chronic diseases. Due to the rise in the elderly population, age-dependent neurodegenerative disorders are becoming increasingly prevalent. The available treatment options only provide symptomatic relief and do not cure the underlying cause of the disease. Therefore, it has become imperative to discover new markers and therapies to modulate the course of disease progression and develop better treatment options for the affected individuals. Growing evidence indicates that neuroinflammation is a common factor and one of the main inducers of neuronal damage and degeneration. Galectins (Gals) are a class of ß-galactoside-binding proteins (lectins) ubiquitously expressed in almost all vital organs. Gals modulate various cellular responses and regulate significant biological functions, including immune response, proliferation, differentiation, migration, and cell growth, through their interaction with glycoproteins and glycolipids. In recent years, extensive research has been conducted on the Gal superfamily, with Gal-1, Gal-3, and Gal-9 in prime focus. Their roles have been described in modulating neuroinflammation and neurodegenerative processes. In this review, we discuss the role of Gals in the causation and progression of neurodegenerative disorders. We describe the role of Gals in microglia and astrocyte modulation, along with their pro- and anti-inflammatory functions. In addition, we discuss the potential use of Gals as a novel therapeutic target for neuroinflammation and restoring tissue damage in neurodegenerative diseases.
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Galectinas , Doenças Neurodegenerativas , Idoso , Anti-Inflamatórios , Galectinas/metabolismo , Glicolipídeos , Humanos , Microglia/metabolismo , Doenças Neurodegenerativas/tratamento farmacológicoRESUMO
Present research was planned to assess the in vitro and in vivo anti-arthritic potential of Caralluma tuberculata N. E. Brown. methanolic (CTME) and aqueous (CTAQ) extracts. Chemical characterization was done by high-performance liquid chromatography and gas chromatography−mass spectrometry analysis. The Complete Freund's Adjuvant (CFA) was injected in left hind paw of rat at day 1 and dosing at 150, 300 and 600 mg/kg was started on the 8th day via oral gavage in all groups except normal and disease control rats (which were given distilled water), whereas methotrexate (intraperitoneal; 1 mg/kg/mL) was administered to standard control. The CTME and CTAQ exerted significant (p < 0.01−0.0001) in vitro anti-arthritic action. Both extracts notably reduced paw edema, and restored weight loss, immune organs weight, arthritic score, RBCs, ESR, platelet count, rheumatoid factor (RF), C-reactive protein, and WBCs in treated rats. The plant extracts showed significant (p < 0.05−0.0001) downregulation of tumor necrosis factor-α, Interleukin-6, -1ß, NF-κB, and cyclooxygenase-2, while notably upregulated IL-4, IL-10, I-κBα in contrast to disease control rats. The plant extracts noticeably (p < 0.001−0.0001) restored the superoxide dismutase and catalase activities and MDA levels in treated rats. Both extracts exhibited significant anti-arthritic potential. The promising potential was exhibited by both extracts probably due to phenolic, and flavonoids compounds.
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Apocynaceae , Artrite Experimental , Animais , Anti-Inflamatórios/uso terapêutico , Artrite Experimental/patologia , Proteína C-Reativa , Catalase , Ciclo-Oxigenase 2 , Flavonoides/uso terapêutico , Adjuvante de Freund , Interleucina-10 , Interleucina-4 , Interleucina-6 , Metotrexato/uso terapêutico , NF-kappa B , Extratos Vegetais/uso terapêutico , Ratos , Fator Reumatoide , Superóxido Dismutase/uso terapêutico , Fator de Necrose Tumoral alfa , ÁguaRESUMO
Phenolic acids (PAs) are one of the utmost prevalent classes of plant-derived bioactive chemicals. They have a specific taste and odor, and are found in numerous medicinal and food plants, such as Cynomorium coccineum L., Prunus domestica (L.), and Vitis vinifera L. Their biosynthesis, physical and chemical characteristics and structure-activity relationship are well understood. These phytochemicals and their derivatives exert several bioactivities including but not limited to anticancer, cardioprotective, anti-inflammatory, immune-regulatory and anti-obesity properties. They are strong antioxidants because of hydroxyl groups which play pivotal role in their anticancer, anti-inflammatory and cardioprotective potential. They may play significant role in improving human health owing to anticarcinogenic, anti-arthritis, antihypertensive, anti-stroke, and anti-atherosclerosis activities, as several PAs have demonstrated biological activities against these disease during in vitro and in vivo studies. These PAs exhibited anticancer action by promoting apoptosis, targeting angiogenesis, and reducing abnormal cell growth, while anti-inflammatory activity was attributed to reducing proinflammatory cytokines. Pas exhibited anti-atherosclerotic activity via inhibition of platelets. Moreover, they also reduced cardiovascular complications such as myocardial infarction and stroke by activating Paraoxonase 1. The present review focuses on the plant sources, structure activity relationship, anticancer, anti-inflammatory and cardioprotective actions of PAs that is attributed to modulation of oxidative stress and signal transduction pathways, along with highlighting their mechanism of actions in disease conditions. Further, preclinical and clinical studies must be carried out to evaluate the mechanism of action and drug targets of PAs to understand their therapeutic actions and disease therapy in humans, respectively.