RESUMEN
Blood-brain barrier (BBB) disruption is a major pathophysiological event of ischemic stroke. Brain microvascular endothelial cells are critical to maintain homeostasis between central nervous system and periphery. Resveratrol protects against ischemic stroke. 3,3',4,5'-tetramethoxy-trans-stilbene (3,3',4,5'-TMS) and 3,4',5-trimethoxy-trans-stilbene (3,4',5-TMS) are resveratrol derivatives with addition of methoxy groups, showing better pharmacokinetic performance. We aimed to explore their protective effects and underlying mechanisms. Oxygen-glucose deprivation (OGD) model was applied in bEnd.3 cell line, mouse brain microvascular endothelium to mimic ischemia. The cells were pre-treated with 3,3',4,5'-TMS or 3,4',5-TMS (1 and 5 µM, 24 h) and then subjected to 2-h OGD injury. Cell viability, levels of proinflammatory cytokines and reactive oxygen species (ROS), and protein expressions were measured by molecular assays and fluorescence staining. OGD injury triggered cell death, inflammatory responses, ROS production and nuclear factor-kappa B (NF-κB) signalling pathway. These impairments were remarkably attenuated by the two stilbenes, 3,3',4,5'-TMS and 3,4',5-TMS. They also alleviated endothelial barrier injuries through upregulating the expression of tight junction proteins. Moreover, 3,3',4,5'-TMS and 3,4',5-TMS activated 5' adenosine monophosphate-activated protein kinase (AMPK) and endothelial nitric oxide synthase (eNOS). Overall, 3,3',4,5'-TMS and 3,4',5-TMS exert protective effects against OGD damage through suppressing cell death, inflammatory responses, oxidative stress, as well as BBB disruption on bEnd.3 cells.
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Encéfalo , Supervivencia Celular , Células Endoteliales , Glucosa , Oxígeno , Especies Reactivas de Oxígeno , Estilbenos , Estilbenos/farmacología , Animales , Glucosa/metabolismo , Ratones , Células Endoteliales/metabolismo , Células Endoteliales/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Oxígeno/metabolismo , Línea Celular , Encéfalo/metabolismo , Encéfalo/efectos de los fármacos , Encéfalo/patología , Supervivencia Celular/efectos de los fármacos , Barrera Hematoencefálica/efectos de los fármacos , Barrera Hematoencefálica/metabolismo , Estrés Oxidativo/efectos de los fármacos , Citocinas/metabolismo , Transducción de Señal/efectos de los fármacos , Hipoxia de la Célula/efectos de los fármacosRESUMEN
BACKGROUND: The interleukin-2 (IL-2) family of cytokines, including IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21, are pivotal regulators of the immune response, impacting both innate and adaptive immunity. Understanding their molecular characteristics, receptor interactions, and signalling pathways is essential for elucidating their roles in health and disease. OBJECTIVES: This review provides a comprehensive overview of the IL-2 family of cytokines, highlighting their molecular biology, receptor interactions, and signalling mechanisms. Furthermore, it explores the involvement of IL-2 family cytokines in the pathogenesis of chronic respiratory diseases, with a specific focus on chronic obstructive pulmonary disease (COPD) and asthma. METHODS: A thorough literature review was conducted to gather insights into the molecular biology, receptor interactions, and signalling pathways of IL-2 family cytokines. Additionally, studies investigating the roles of these cytokines in chronic respiratory diseases, particularly COPD and asthma, were analysed to discern their implications in wider pathophysiology of disease. RESULTS: IL-2 family cytokines exert pleiotropic effects on immune cells, modulating cellular proliferation, differentiation, and survival. Dysregulation of IL-2 family cytokines has been implicated in the pathogenesis of chronic respiratory illnesses, including COPD and asthma. Elevated levels of IL-2 and IL-9 have been associated with disease severity in COPD, while IL-4 and IL-9 play crucial roles in asthma pathogenesis by promoting airway inflammation and remodelling. CONCLUSION: Understanding the intricate roles of IL-2 family cytokines in chronic respiratory diseases provides valuable insights into potential therapeutic targets for these conditions. Targeting specific cytokines or their receptors may offer novel treatment modalities to attenuate disease progression and improve clinical outcomes in patients with COPD and asthma.
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Asma , Interleucina-2 , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Asma/inmunología , Asma/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/inmunología , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Interleucina-2/metabolismo , Transducción de Señal , AnimalesRESUMEN
Sciatica characterized by irritation, inflammation, and compression of the lower back nerve, is considered one of the most common back ailments globally. Currently, the therapeutic regimens for sciatica are experiencing a paradigm shift from the conventional pharmacological approach toward exploring potent phytochemicals from medicinal plants. There is a dire need to identify novel phytochemicals with anti-neuropathic potential. This review aimed to identify the potent phytochemicals from diverse medicinal plants capable of alleviating neuropathic pain associated with sciatica. This review describes the pathophysiology of sciatic nerve pain, its cellular mechanisms, and the pharmacological potential of various plants and phytochemicals using animal-based models of sciatic nerve injury-induced pain. Extensive searches across databases such as Medline, PubMed, Web of Science, Scopus, ScienceDirect, and Google Scholar were conducted. The findings highlights 39 families including Lamiaceae, Asteraceae, Fabaceae, and Apocyanaceae and Cucurbitaceae, effectively treating sciatic nerve injury-induced pain. Flavonoids made up 53% constituents, phenols and terpenoids made up 15%, alkaloids made up 13%, and glycosides made up 6% to be used in neuorpathic pain. Phytochemicals derived from various medicinal plants can serve as potential therapeutic targets for both acute and chronic sciatic injury-induced neuropathic pain.
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Neuralgia , Plantas Medicinales , Neuropatía Ciática , Ciática , Animales , Humanos , Plantas Medicinales/química , Ciática/tratamiento farmacológico , Ciática/etiología , Neuralgia/tratamiento farmacológico , Neuralgia/etiología , Neuropatía Ciática/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Fitoquímicos/farmacología , Fitoquímicos/uso terapéutico , Fitoquímicos/química , Fitoterapia , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Extractos Vegetales/químicaRESUMEN
As a critical cause of human dysfunctionality, hepatic failure leads to approximately two million deaths per year and is on the rise. Considering multiple inflammatory, oxidative, and apoptotic mechanisms behind hepatotoxicity, it urges the need for finding novel multi-targeting agents. Curcumin is a phenolic compound with anti-inflammatory, antioxidant, and anti-apoptotic roles. Curcumin possesses auspicious health benefits and protects against several diseases with exceptional safety and tolerability. This review focused on the hepatoprotective mechanisms of curcumin. The need to develop novel delivery systems of curcumin (e.g., nanoparticles, self-micro emulsifying, lipid-based colloids, solid lipid nanoparticles, cyclodextrin inclusion, phospholipid complexes, and nanoemulsions) is also considered.
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Curcumina , Curcumina/farmacología , Curcumina/química , Humanos , Animales , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Antioxidantes/farmacología , Antioxidantes/química , Hígado/efectos de los fármacos , Hígado/patología , Sustancias Protectoras/farmacología , Sustancias Protectoras/química , Nanopartículas , Apoptosis/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacosRESUMEN
Recently, malignant neoplasms have growingly caused human morbidity and mortality. Head and neck cancer (HNC) constitutes a substantial group of malignancies occurring in various anatomical regions of the head and neck, including lips, mouth, throat, larynx, nose, sinuses, oropharynx, hypopharynx, nasopharynx, and salivary glands. The present study addresses the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway as a possible therapeutic target in cancer therapy. Finding new multitargeting agents capable of modulating PI3K/Akt/mTOR and cross-linked mediators could be viewed as an effective strategy in combating HNC. Recent studies have introduced phytochemicals as multitargeting agents and rich sources for finding and developing new therapeutic agents. Phytochemicals have exhibited immense anticancer effects, including targeting different stages of HNC through the modulation of several signaling pathways. Moreover, phenolic/polyphenolic compounds, alkaloids, terpenes/terpenoids, and other secondary metabolites have demonstrated promising anticancer activities because of their diverse pharmacological and biological properties like antiproliferative, antineoplastic, antioxidant, and anti-inflammatory activities. The current review is mainly focused on new therapeutic strategies for HNC passing through the PI3K/Akt/mTOR pathway as new strategies in combating HNC.
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Neoplasias de Cabeza y Cuello , Fosfatidilinositol 3-Quinasas , Fitoquímicos , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Serina-Treonina Quinasas TOR , Humanos , Serina-Treonina Quinasas TOR/metabolismo , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Transducción de Señal/efectos de los fármacos , Fitoquímicos/farmacología , Fitoquímicos/química , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Antineoplásicos Fitogénicos/farmacologíaRESUMEN
Brain-computer interface (BCI) systems include signal acquisition, preprocessing, feature extraction, classification, and an application phase. In fNIRS-BCI systems, deep learning (DL) algorithms play a crucial role in enhancing accuracy. Unlike traditional machine learning (ML) classifiers, DL algorithms eliminate the need for manual feature extraction. DL neural networks automatically extract hidden patterns/features within a dataset to classify the data. In this study, a hand-gripping (closing and opening) two-class motor activity dataset from twenty healthy participants is acquired, and an integrated contextual gate network (ICGN) algorithm (proposed) is applied to that dataset to enhance the classification accuracy. The proposed algorithm extracts the features from the filtered data and generates the patterns based on the information from the previous cells within the network. Accordingly, classification is performed based on the similar generated patterns within the dataset. The accuracy of the proposed algorithm is compared with the long short-term memory (LSTM) and bidirectional long short-term memory (Bi-LSTM). The proposed ICGN algorithm yielded a classification accuracy of 91.23 ± 1.60%, which is significantly (p < 0.025) higher than the 84.89 ± 3.91 and 88.82 ± 1.96 achieved by LSTM and Bi-LSTM, respectively. An open access, three-class (right- and left-hand finger tapping and dominant foot tapping) dataset of 30 subjects is used to validate the proposed algorithm. The results show that ICGN can be efficiently used for the classification of two- and three-class problems in fNIRS-based BCI applications.
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Algoritmos , Interfaces Cerebro-Computador , Aprendizaje Profundo , Redes Neurales de la Computación , Espectroscopía Infrarroja Corta , Humanos , Espectroscopía Infrarroja Corta/métodos , Masculino , Adulto , Femenino , Adulto Joven , Encéfalo/fisiología , Encéfalo/diagnóstico por imagenRESUMEN
BACKGROUND: Dental pathogens play a crucial role in oral health issues, including tooth decay, gum disease, and oral infections, and recent research suggests a link between these pathogens and oral cancer initiation and progression. Innovative therapeutic approaches are needed due to antibiotic resistance concerns and treatment limitations. METHODS: We synthesized and analyzed piperine-coated zinc oxide nanoparticles (ZnO-PIP NPs) using UV spectroscopy, SEM, XRD, FTIR, and EDAX. Antioxidant and antimicrobial effectiveness were evaluated through DPPH, ABTS, and MIC assays, while the anticancer properties were assessed on KB oral squamous carcinoma cells. RESULTS: ZnO-PIP NPs exhibited significant antioxidant activity and a MIC of 50 µg/mL against dental pathogens, indicating strong antimicrobial properties. Interaction analysis revealed high binding affinity with dental pathogens. ZnO-PIP NPs showed dose-dependent anticancer activity on KB cells, upregulating apoptotic genes BCL2, BAX, and P53. CONCLUSIONS: This approach offers a multifaceted solution to combatting both oral infections and cancer, showcasing their potential for significant advancement in oral healthcare. It is essential to acknowledge potential limitations and challenges associated with the use of ZnO NPs in clinical applications. These may include concerns regarding nanoparticle toxicity, biocompatibility, and long-term safety. Further research and rigorous testing are warranted to address these issues and ensure the safe and effective translation of ZnO-PIP NPs into clinical practice.
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Alcaloides , Apoptosis , Benzodioxoles , Biopelículas , Neoplasias de la Boca , Piperidinas , Alcamidas Poliinsaturadas , Óxido de Zinc , Proteína X Asociada a bcl-2 , Humanos , Alcaloides/farmacología , Antineoplásicos/farmacología , Antioxidantes/farmacología , Apoptosis/efectos de los fármacos , Proteína X Asociada a bcl-2/metabolismo , Proteína X Asociada a bcl-2/efectos de los fármacos , Benzodioxoles/farmacología , Biopelículas/efectos de los fármacos , Línea Celular Tumoral , Células KB , Nanopartículas del Metal/uso terapéutico , Pruebas de Sensibilidad Microbiana , Microscopía Electrónica de Rastreo , Neoplasias de la Boca/tratamiento farmacológico , Neoplasias de la Boca/patología , Nanopartículas , Piperidinas/farmacología , Alcamidas Poliinsaturadas/farmacología , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Proteína p53 Supresora de Tumor/efectos de los fármacos , Difracción de Rayos X , Óxido de Zinc/farmacologíaRESUMEN
Hypoxic preconditioning has been demonstrated to increase the resistance of neural stem cells (NSCs) to hypoxic conditions, as well as to improve their capacity for differentiation and neurogenesis. Extracellular vesicles (EVs) have recently emerged as critical mediators of cell-cell communication, but their role in this hypoxic conditioning is presently unknown. Here, we demonstrated that three hours of hypoxic preconditioning triggers significant neural stem cell EV release. Proteomic profiling of EVs from normal and hypoxic preconditioned neural stem cells identified 20 proteins that were upregulated and 22 proteins that were downregulated after hypoxic preconditioning. We also found an upregulation of some of these proteins by qPCR, thus indicating differences also at the transcript level within the EVs. Among the upregulated proteins are CNP, Cyfip1, CASK, and TUBB5, which are well known to exhibit significant beneficial effects on neural stem cells. Thus, our results not only show a significant difference of protein cargo in EVs consequent to hypoxic exposure, but identify several candidate proteins that might play a pivotal role in the cell-to-cell mediated communication underlying neuronal differentiation, protection, maturation, and survival following exposure to hypoxic conditions.
RESUMEN
Though the iconic stilbene resveratrol and its related dimers constitute a top storyline in the field of natural product research, resveratrol oligomers (condensation >2) have been left aside despite their higher biological activity compared to that of the monomers. This situation largely results from the difficulty of getting them in sufficient quantities to enable evaluation of their biological properties in vivo. We present here a synthetic and critical analysis of the methods used for the production of high molecular-ordered stilbene oligomers of potential biomedical interest, gathering the most salient data regarding the approaches employed to prepare them by total synthesis, use of biomimetic approaches or through plant systems.
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Estilbenos , Resveratrol , Estilbenos/farmacología , CatálisisRESUMEN
BACKGROUND: Receptor-interacting protein kinase 1 (RIPK1) is a key mediator of regulated cell death (including apoptosis and necroptosis) and inflammation, both drivers of COPD pathogenesis. We aimed to define the contribution of RIPK1 kinase-dependent cell death and inflammation in the pathogenesis of COPD. METHODS: We assessed RIPK1 expression in single-cell RNA sequencing (RNA-seq) data from human and mouse lungs, and validated RIPK1 levels in lung tissue of COPD patients via immunohistochemistry. Next, we assessed the consequences of genetic and pharmacological inhibition of RIPK1 kinase activity in experimental COPD, using Ripk1 S25D/S25D kinase-deficient mice and the RIPK1 kinase inhibitor GSK'547. RESULTS: RIPK1 expression increased in alveolar type 1 (AT1), AT2, ciliated and neuroendocrine cells in human COPD. RIPK1 protein levels were significantly increased in airway epithelium of COPD patients compared with never-smokers and smokers without airflow limitation. In mice, exposure to cigarette smoke (CS) increased Ripk1 expression similarly in AT2 cells, and further in alveolar macrophages and T-cells. Genetic and/or pharmacological inhibition of RIPK1 kinase activity significantly attenuated airway inflammation upon acute and subacute CS exposure, as well as airway remodelling, emphysema, and apoptotic and necroptotic cell death upon chronic CS exposure. Similarly, pharmacological RIPK1 kinase inhibition significantly attenuated elastase-induced emphysema and lung function decline. Finally, RNA-seq on lung tissue of CS-exposed mice revealed downregulation of cell death and inflammatory pathways upon pharmacological RIPK1 kinase inhibition. CONCLUSIONS: RIPK1 kinase inhibition is protective in experimental models of COPD and may represent a novel promising therapeutic approach.
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Enfisema , Enfermedad Pulmonar Obstructiva Crónica , Enfisema Pulmonar , Humanos , Ratones , Animales , Pulmón , Muerte Celular , Inflamación/metabolismo , Ratones Endogámicos C57BL , Proteína Serina-Treonina Quinasas de Interacción con Receptores/genética , Proteína Serina-Treonina Quinasas de Interacción con Receptores/metabolismoRESUMEN
Most human infectious diseases are caused by microorganisms growing as biofilms. These three-dimensional self-organized communities are embedded in a dense matrix allowing microorganisms to persistently inhabit abiotic and biotic surfaces due to increased resistance to both antibiotics and effectors of the immune system. Consequently, there is an urgent need for novel strategies to control biofilm-associated infections. Natural products offer a vast array of chemical structures and possess a wide variety of biological properties; therefore, they have been and continue to be exploited in the search for potential biofilm inhibitors with a specific or multi-locus mechanism of action. This review provides an updated discussion of the major bioactive compounds isolated from several natural sources - such as plants, lichens, algae, microorganisms, animals, and humans - with the potential to inhibit biofilm formation and/or to disperse established biofilms by bacterial pathogens. Despite the very large number of bioactive products, their exact mechanism of action often remains to be clarified and, in some cases, the identity of the active molecule is still unknown. This knowledge gap should be filled thus allowing development of these products not only as novel drugs to combat bacterial biofilms, but also as antibiotic adjuvants to restore the therapeutic efficacy of current antibiotics.
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Bacterias , Productos Biológicos , Animales , Humanos , Biopelículas , Antibacterianos/química , Productos Biológicos/farmacologíaRESUMEN
Autophagy is defined as a "self-digestion" signal, and it is a cell death mechanism its primary function is degrading toxic agents and aged organelles to ensure homeostasis in cells. The basic leve ls of autophagy are found in cells, and when its levels exceed to standard threshold, cell death induction is observed. Autophagy dysregulation in cancer has been well-documented, and regulation of this pathway by epigenetic factors, especially microRNAs (miRNAs), is interesting and noteworthy. miRNAs are considered short endogenous RNAs that do not encode functional proteins, and they are essential regulators of cell death pathways such as apoptosis, necroptosis, and autophagy. Accumulating data has revealed miRNA dysregulation (upregulation or downregulation) during tumor progression, and their therapeutic manipulation provides new insight into cancer therapy. miRNA/autophagy axis in human cancers has been investigated an exciting point is the dual function of both autophagy and miRNAs as oncogenic and onco-suppressor factors. The stimulation of pro-survival autophagy by miRNAs can increase the survival rate of tumor cells and mediates cancer metastasis via EMT inductionFurthermore, pro-death autophagy induction by miRNAs has a negative impact on the viability of tumor cells and decreases their survival rate. The miRNA/autophagy axis functions beyond regulating the growth and invasion of tumor cells, and they can also affect drug resistance and radio-resistance. These subjects are covered in the current review regarding the new updates provided by recent experiments.
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MicroARNs , Neoplasias , Humanos , Anciano , MicroARNs/genética , Transducción de Señal/fisiología , Neoplasias/patología , Carcinogénesis/genética , Autofagia/genética , Digestión , Regulación Neoplásica de la Expresión GénicaRESUMEN
The field of non-coding RNA (ncRNA) has made significant progress in understanding the pathogenesis of diseases and has broadened our knowledge towards their targeting, especially in cancer therapy. ncRNAs are a large family of RNAs with microRNAs (miRNAs) being one kind of endogenous RNA which lack encoded proteins. By now, miRNAs have been well-coined in pathogenesis and development of cancer. The current review focuses on the role of miR-21 in cancers and its association with tumor progression. miR-21 has both oncogenic and onco-suppressor functions and most of the experiments are in agreement with the tumor-promoting function of this miRNA. miR-21 primarily decreases PTEN expression to induce PI3K/Akt signaling in cancer progression. Overexpression of miR-21 inhibits apoptosis and is vital for inducing pro-survival autophagy. miR-21 is vital for metabolic reprogramming and can induce glycolysis to enhance tumor progression. miR-21 stimulates EMT mechanisms and increases expression of MMP-2 and MMP-9 thereby elevating tumor metastasis. miR-21 is a target of anti-cancer agents such as curcumin and curcumol and its down-regulation impairs tumor progression. Upregulation of miR-21 results in cancer resistance to chemotherapy and radiotherapy. Increasing evidence has revealed the role of miR-21 as a biomarker as it is present in both the serum and exosomes making them beneficial biomarkers for non-invasive diagnosis of cancer.
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Carcinogénesis , MicroARNs , Neoplasias , Humanos , Carcinogénesis/genética , Línea Celular Tumoral , Proliferación Celular/genética , Transformación Celular Neoplásica , Relevancia Clínica , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , MicroARNs/metabolismo , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Fosfatidilinositol 3-Quinasas/metabolismoRESUMEN
Malignant melanoma is the most dangerous type of skin cancer. It is becoming more common globally and is increasingly resistant to treatment options. Despite extensive research into its pathophysiology, there are still no proven cures for metastatic melanoma. Unfortunately, current treatments are frequently ineffective and costly, and have several adverse effects. Natural substances have been extensively researched for their anti-MM capabilities. Chemoprevention and adjuvant therapy with natural products is an emerging strategy to prevent, cure or treat melanoma. Numerous prospective drugs are found in aquatic species, providing a plentiful supply of lead cytotoxic chemicals for cancer treatment. Anticancer peptides are less harmful to healthy cells and cure cancer through several different methods, such as altered cell viability, apoptosis, angiogenesis/metastasis suppression, microtubule balance disturbances and targeting lipid composition of the cancer cell membrane. This review addresses marine peptides as effective and safe treatments for MM and details their molecular mechanisms of action.
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Antineoplásicos , Melanoma , Neoplasias Cutáneas , Humanos , Melanoma/tratamiento farmacológico , Melanoma/patología , Neoplasias Cutáneas/tratamiento farmacológico , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Péptidos/farmacología , Péptidos/uso terapéutico , Apoptosis , Melanoma Cutáneo MalignoRESUMEN
Mangifera indica L., also known as mango, is a tropical fruit that belongs to the Anacardiaceae family and is prized for its juiciness, unique flavour, and worldwide popularity. The current study aimed to probe into antidepressant power (ADP) of MIS in animals and confirmation of ADP with in silico induced-fit molecular docking. The depression model was prepared by exposing mice to various stressors from 9:00 am to 2:00 pm during 42 days study period. MIS extract and fluoxetine were given daily for 30 min before exposing animals to stressors. ADP was evaluated by various behavioural tests and biochemical analysis. Results showed increased physical activity in mice under behavioural tests, plasma nitrite and malondialdehyde (MDA) levels and monoamine oxidase A (MAO-A) activity decreased dose-dependently in MIS treated mice and superoxide dismutases (SOD) levels increased in treated groups as compared to disease control. With the peculiar behaviour and significant interactions of the functional residues of target proteins with selected ligands along with the best absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties, it is concluded that catechin could be the best MAO-A inhibitor at a binding energy of -8.85 kcal/mol, and two hydrogen bonds were generated with Cys406 (A) and Gly443 (A) residues of the active binding site of MAO-A enzyme. While catechin at -6.86 kcal/mol generated three hydrogen bonds with Ala263 (A) and Gly434 (A) residues of the active site of monoamine oxidase B (MAO-B) enzyme and stabilized the best conformation. Therefore, it is highly recommended to test the selected lead-like compound catechin in the laboratory with biological system analysis to confirm its activity as MAO-A and MAO-B inhibitors so it can be declared as one of the novel therapeutic options with anti-depressant activity. Our findings concluded that M. indica seeds could be a significant and alternative anti-depressant therapy.
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Catequina , Mangifera , Ratones , Animales , Antidepresivos/farmacología , Antidepresivos/uso terapéutico , Antidepresivos/química , Mangifera/metabolismo , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Extractos Vegetales/química , Simulación del Acoplamiento Molecular , Catequina/análisis , Inhibidores de la Monoaminooxidasa/farmacología , Monoaminooxidasa/metabolismo , Semillas/química , Fitoquímicos/farmacología , Fitoquímicos/uso terapéuticoRESUMEN
Aggression, a highly prevalent behavior among all the psychological disorders having strong association with psychiatric imbalance, neuroendocrine changes and neurological disturbances (including oxidative stress & neuroinflammation) require both pharmacological and non-pharmacological treatments. Focusing the preclinical neuroendocrine determinants of aggression, this interventional study was designed to elucidate the curative effect of antioxidants on aggression in male mice. Adult albino male mice (n = 140) randomly divided into two main treatment groups for α-lipoic acid (ALA) and silymarin with 5 subgroups (n = 10) for each curative study, namely control, disease (aggression-induced), standard (diazepam, 2.5 mg/kg), low dose (100 mg/kg) and high dose (200 mg/kg) treatment groups of selected antioxidants. Resident-intruder paradigm and levodopa (L-dopa 375 mg/kg, p.o.) induced models were used for aggression. Effect of antioxidant treatment (i.e., 21 days bid) on aggression was assessed by evaluating the changes in aggressive behavior, oxidative stress biomarkers superoxide dismutase, catalase, glutathione, nitrite and malondialdehyde (SOD, CAT, GSH, nitrite & MDA), neurotransmitters (dopamine, nor-adrenaline and serotonin), pro-inflammatory cytokines tumor necrosis factor-α and interleukin- 6 (TNF-α & IL-6) along with serum testosterone examination. This study showed potential ameliorative effect on aggressive behavior with both low (100 mg/kg) and high (200 mg/kg) doses of antioxidants (ALA & silymarin). Resident-intruder or L-dopa induced aggression in male mice was more significantly tuned with ALA treatment than silymarin via down regulating both oxidative stress and inflammatory biomarkers. ALA also exhibited notable effects in managing aggression-induced disturbances on plasma testosterone levels. In conclusion, ALA is more effective than silymarin in attenuating aggression in mice.
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Silimarina , Ácido Tióctico , Masculino , Ratones , Animales , Ácido Tióctico/farmacología , Ácido Tióctico/uso terapéutico , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Antioxidantes/metabolismo , Silimarina/farmacología , Silimarina/uso terapéutico , Levodopa/farmacología , Nitritos/farmacología , Estrés Oxidativo , Glutatión/metabolismo , Agresión , Biomarcadores/metabolismo , TestosteronaRESUMEN
Usually, in aerobic metabolism, natural materials including nucleic acids, proteins, and lipids can experience auxiliary injury by oxidative responses. This damage produced by reactive oxygen/nitrogen species has been identified as "oxidative stress." As a natural polyphenol got from red wine and peanuts, resveratrol is one of the most eminent anti-aging mixtures. Based on many studies', resveratrol hinders destructive effects of inflammatory causes and reactive oxygen radicals in several tissues. The nuclear erythroid 2-related factor 2 is a factor related to transcription with anti-inflammatory, antioxidant possessions which is complicated by enzyme biotransformation and biosynthesis of lipids and carbohydrates. This review provides current understanding and information about the character of resveratrol against oxidative stress and regulation of inflammation via Nrf2 signaling pathway.
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Factor 2 Relacionado con NF-E2 , Estrés Oxidativo , Humanos , Resveratrol/uso terapéutico , Factor 2 Relacionado con NF-E2/metabolismo , Transducción de Señal , Inflamación/tratamiento farmacológico , Especies Reactivas de Oxígeno/metabolismo , Especies de Nitrógeno Reactivo , LípidosRESUMEN
Gait and balance are an intricate interplay between the brain, nervous system, sensory organs, and musculoskeletal system. They are greatly influenced by the type of footwear, walking patterns, and surface. This exploratory study examines the effects of the Infinity Walk, pronation, and footwear conditions on brain effective connectivity patterns. A continuous-wave functional near-infrared spectroscopy device collected data from five healthy participants. A highly computationally efficient connectivity model based on the Grange causal relationship between the channels was applied to data to find the effective relationship between inter- and intra-hemispheric brain connectivity. Brain regions of interest (ROI) were less connected during the barefoot condition than during other complex walks. Conversely, the highest interconnectedness between ROI was observed while wearing flat insoles and medially wedged sandals, which is a relatively difficult type of footwear to walk in. No statistically significant (p-value <0.05) effect on connectivity patterns was observed during the corrected pronated posture. The regions designated as motoric, sensorimotor, and temporal became increasingly connected with difficult walking patterns and footwear conditions. The Infinity Walk causes effective bidirectional connections between ROI across all conditions and both hemispheres. Due to its repetitive pattern, the Infinity Walk is a good test method, particularly for neuro-rehabilitation and motoric learning experiments.
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Marcha , Caminata , Humanos , Caminata/fisiología , Marcha/fisiología , Encéfalo , Postura , Análisis Espectral , ZapatosRESUMEN
Mentha longifolia is a valuable medicinal and aromatic plant that belongs to Lamiaceae family. This study looked at the antibacterial effects of M. longifolia essential oil and pulegone in edible coatings made of chitosan and alginate on the growth of Staphylococcus aureus, Listeria monocytogenes, and Escherichia coli in cheese. For this purpose, first fresh mint plant was collected from the cold region of Jiroft in Kerman province. Plant samples were dried in the shade at ambient temperature, and essential oil was prepared using Clevenger. The essential oil was analyzed by gas chromatography using mass spectrometric (GC/MS) detection. The major composition of M. longifolia oil was pulegone (26.07%), piperitone oxide (19.72%), and piperitone (11.88%). The results showed that adding M. longifolia essential oils and pulegone to edible coatings significantly reduced the growth of bacteria during storage. The bacterial population decreased by increasing the concentration of chitosan, M. longifolia, and pulegone in edible coatings. When the effects of pulegone and M. longifolia essential oils on bacteria were compared, it was found that pulegone had a stronger effect on bacterial population reduction. Coating treatments showed more antibacterial activity on E. coli than other bacteria. In general, the results of this research showed that alginate and chitosan coatings along with M. longifolia essential oil and its active ingredient pulegone had antibacterial effects against S. aureus, L. monocytogenes, and E. coli in cheese.
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Queso , Quitosano , Películas Comestibles , Mentha , Aceites Volátiles , Aceites Volátiles/química , Mentha/química , Quitosano/farmacología , Monoterpenos/química , Alginatos/farmacología , Staphylococcus aureus , Escherichia coli , Queso/análisis , Bacterias , Antibacterianos/farmacología , Antibacterianos/análisisRESUMEN
Due to genetic changes in DNA (deoxyribonucleic acid) sequences, cancer continues to be the second most prevalent cause of death. The traditional target-directed approach, which is confronted with the importance of target function in healthy cells, is one of the most significant challenges in anticancer research. Another problem with cancer cells is that they experience various mutations, changes in gene duplication, and chromosomal abnormalities, all of which have a direct influence on the potency of anticancer drugs at different developmental stages. All of these factors combine to make cancer medication development difficult, with low clinical licensure success rates when compared to other therapy categories. The current review focuses on the pathophysiology and molecular aspects of common cancer types. Currently, the available chemotherapeutic drugs, also known as combination chemotherapy, are associated with numerous adverse effects, resulting in the search for herbal-based alternatives that attenuate resistance due to cancer therapy and exert chemo-protective actions. To provide new insights, this review updated the list of key compounds that may enhance the efficacy of cancer treatment.