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1.
Curr Drug Targets ; 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38752634

RESUMEN

Diabetes Mellitus (DM) is referred to as hyperglycemia in either fasting or postprandial phases. Oxidative stress, which is defined by an excessive amount of reactive oxygen species (ROS) production, increased exposure to external stress, and an excessive amount of the cellular defense system against them, results in cellular damage. Increased DNA damage is one of the main causes of genomic instability, and genetic changes are an underlying factor in the emergence of cancer. Through covalent connections with DNA and proteins, quercetin has been demonstrated to offer protection against the creation of oxidative DNA damage. It has been found that quercetin shields DNA from possible oxidative stress-related harm by reducing the production of ROS. Therefore, Quercetin helps to lessen DNA damage and improve the ability of DNA repair mechanisms. This review mainly focuses on the role of quercetin in repairing DNA damage and compensating for drug resistance in diabetic patients. Data on the target topic was obtained from major scientific databases, including SpringerLink, Web of Science, Google Scholar, Medline Plus, PubMed, Science Direct, and Elsevier. In preclinical studies, quercetin guards against DNA deterioration by regulating the degree of lipid peroxidation and enhancing the antioxidant defense system. By reactivating antioxidant enzymes, decreasing ROS levels, and decreasing the levels of 8-hydroxydeoxyguanosine, Quercetin protects DNA from oxidative damage. In clinical studies, it was found that quercetin supplementation was related to increased antioxidant capacity and decreased risk of type 2 diabetes mellitus in the experimental group as compared to the placebo group. It is concluded that quercetin has a significant role in DNA repair in order to overcome drug resistance in diabetes.

2.
Vascul Pharmacol ; 152: 107213, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37625763

RESUMEN

Aging is one of the most promising risk factors for vascular diseases, however, the precise mechanisms mediating aging-related pathologies are not fully understood. Amyloid beta (Aß), a peptide produced by the proteolytic processing of amyloid precursor protein (APP), is known as a key mediator of brain damage involved in the pathogenesis of Alzheimer's disease (AD). Recently, it was found that the accumulation of Aß in the vascular wall is linked to a range of aging-related vascular pathologies, indicating a potential role of Aß in the pathogenesis of aging-associated vascular diseases. In the present review, we have updated the molecular regulation of Aß in vascular cells and tissues, summarized the relevance of the Aß deposition with vascular aging and diseases, and the role of Aß dysregulation in aging-associated vascular pathologies, including the impaired vascular response, endothelial dysfunction, oxidative stress, and inflammation. This review will provide advanced information in understanding aging-related vascular pathologies and a new avenue to explore therapeutic targets.


Asunto(s)
Péptidos beta-Amiloides , Enfermedades Vasculares , Humanos , Estrés Oxidativo , Inflamación
3.
IEEE Trans Industr Inform ; 19(1): 1030-1038, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37469712

RESUMEN

A fundamental expectation of the stakeholders from the Industrial Internet of Things (IIoT) is its trustworthiness and sustainability to avoid the loss of human lives in performing a critical task. A trustworthy IIoT-enabled network encompasses fundamental security characteristics such as trust, privacy, security, reliability, resilience and safety. The traditional security mechanisms and procedures are insufficient to protect these networks owing to protocol differences, limited update options, and older adaptations of the security mechanisms. As a result, these networks require novel approaches to increase trust-level and enhance security and privacy mechanisms. Therefore, in this paper, we propose a novel approach to improve the trustworthiness of IIoT-enabled networks. We propose an accurate and reliable supervisory control and data acquisition (SCADA) network-based cyberattack detection in these networks. The proposed scheme combines the deep learning-based Pyramidal Recurrent Units (PRU) and Decision Tree (DT) with SCADA-based IIoT networks. We also use an ensemble-learning method to detect cyberattacks in SCADA-based IIoT networks. The non-linear learning ability of PRU and the ensemble DT address the sensitivity of irrelevant features, allowing high detection rates. The proposed scheme is evaluated on fifteen datasets generated from SCADA-based networks. The experimental results show that the proposed scheme outperforms traditional methods and machine learning-based detection approaches. The proposed scheme improves the security and associated measure of trustworthiness in IIoT-enabled networks.

4.
Sensors (Basel) ; 23(14)2023 Jul 21.
Artículo en Inglés | MEDLINE | ID: mdl-37514868

RESUMEN

Cyberattacks in the modern world are sophisticated and can be undetected in a dispersed setting. In a distributed setting, DoS and DDoS attacks cause resource unavailability. This has motivated the scientific community to suggest effective approaches in distributed contexts as a means of mitigating such attacks. Syn Flood is the most common sort of DDoS assault, up from 76% to 81% in Q2, according to Kaspersky's Q3 report. Direct and indirect approaches are also available for launching DDoS attacks. While in a DDoS attack, controlled traffic is transmitted indirectly through zombies to reflectors to compromise the target host, in a direct attack, controlled traffic is sent directly to zombies in order to assault the victim host. Reflectors are uncompromised systems that only send replies in response to a request. To mitigate such assaults, traffic shaping and pushback methods are utilised. The SYN Flood Attack Detection and Mitigation Technique (SFaDMT) is an adaptive heuristic-based method we employ to identify DDoS SYN flood assaults. This study suggested an effective strategy to identify and resist the SYN assault. A decision support mechanism served as the foundation for the suggested (SFaDMT) approach. The suggested model was simulated, analysed, and compared to the most recent method using the OMNET simulator. The outcome demonstrates how the suggested fix improved detection.

6.
ISA Trans ; 132: 146-154, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35764425

RESUMEN

Autonomous systems and the Internet of Things (IoT) have become more sophisticated research areas and entered successfully into various daily living activities such as smart homes & buildings, autonomous cars, drones, robots, etc. A crucial and essential aspect of these systems is the precision and accuracy of the decision-making process, i.e., the decision support system. Likewise, developing a completely autonomous system is an open research problem. This paper proposes a computational intelligence-based prediction and communication mechanism for the independent system where IoT is used as a data collection tool. Initially, energy gauge (EG) devices collect helpful information about neighboring devices in the IoT networks. Then, information about the potential relaying devices is broadcasted by the concerned EG device, which uses every member device to adjust routing path(s) in the autonomous system. Furthermore, every EG device has an embedded computational intelligent decision support system that is used to precisely predict the criticality of a neighboring device (preferably relay) in the autonomous systems. Therefore, every device must ensure data transmission via the most reliable path(s), i.e., avoiding critical devices if possible. A device is assumed critical if either its residual energy or received signal strength indicator value is less than the defined threshold values for the autonomous systems. Additionally, the proposed mechanism has ensured a uniform traffic distribution of the transmitted packets in the autonomous system. The operational applicability of the proposed computational intelligence-enabled prediction mechanism in the autonomous system is verified by comparing it with the existing approaches. Simulation results show that the proposed scheme has enhanced the accuracy of the concerned autonomous systems more than other schemes.

7.
Biomedicines ; 10(12)2022 Dec 08.
Artículo en Inglés | MEDLINE | ID: mdl-36551934

RESUMEN

The rhizomatous plant turmeric, which is frequently used as a spice and coloring ingredient, yields curcumin, a bioactive compound. Curcumin inhibits platelet activation and aggregation and improves platelet count. Platelets dysfunction results in several disorders, including inflammation, atherothrombosis, and thromboembolism. Several studies have proved the beneficial role of curcumin on platelets and hence proved it is an important candidate for the treatment of the aforementioned diseases. Moreover, curcumin is also frequently employed as an anti-inflammatory agent in conventional medicine. In arthritic patients, it has been shown to reduce the generation of pro-inflammatory eicosanoids and to reduce edema, morning stiffness, and other symptoms. Curcumin taken orally also reduced rats' acute inflammation brought on by carrageenan. Curcumin has also been proven to prevent atherosclerosis and platelet aggregation, as well as to reduce angiogenesis in adipose tissue. In the cerebral microcirculation, curcumin significantly lowered platelet and leukocyte adhesion. It largely modulated the endothelium to reduce platelet adhesion. Additionally, P-selectin expression and mice survival after cecal ligation and puncture were improved by curcumin, which also altered platelet and leukocyte adhesion and blood-brain barrier dysfunction. Through regulating many processes involved in platelet aggregation, curcuminoids collectively demonstrated detectable antiplatelet activity. Curcuminoids may therefore be able to prevent disorders linked to platelet activation as possible therapeutic agents. This review article proposes to highlight and discuss the regulatory effects of curcumin on platelets.

8.
Molecules ; 27(13)2022 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-35807304

RESUMEN

Diabetes mellitus is a multifactorial chronic metabolic disorder, characterized by altered metabolism of macro-nutrients, such as fats, proteins, and carbohydrates. Diabetic retinopathy, diabetic cardiomyopathy, diabetic encephalopathy, diabetic periodontitis, and diabetic nephropathy are the prominent complications of diabetes. Inflammatory mediators are primarily responsible for these complications. Curcumin, a polyphenol derived from turmeric, is well known for its anti-oxidant, anti-inflammatory, and anti-apoptotic properties. The regulation of several signaling pathways effectively targets inflammatory mediators in diabetes. Curcumin's anti-inflammatory and anti-oxidative activities against a wide range of molecular targets have been shown to have therapeutic potential for a variety of chronic inflammatory disorders, including diabetes. Curcumin's biological examination has shown that it is a powerful anti-oxidant that stops cells from growing by releasing active free thiol groups at the target location. Curcumin is a powerful anti-inflammatory agent that targets inflammatory mediators in diabetes, and its resistant form leads to better therapeutic outcomes in diabetes complications. Moreover, Curcumin is an anti-oxidant and NF-B inhibitor that may be useful in treating diabetes. Curcumin has been shown to inhibit diabetes-related enzymes, such as a-glucosidase, aldose reductase and aldose reductase inhibitors. Through its anti-oxidant and anti-inflammatory effects, and its suppression of vascular endothelial development and nuclear transcription factors, curcumin has the ability to prevent, or reduce, the course of diabetic retinopathy. Curcumin improves insulin sensitivity by suppressing phosphorylation of ERK/JNK in HG-induced insulin-resistant cells and strengthening the PI3K-AKT-GSK3B signaling pathway. In the present article, we aimed to discuss the anti-inflammatory mechanisms of curcumin in diabetes regulated by various molecular signaling pathways.


Asunto(s)
Curcumina , Diabetes Mellitus , Nefropatías Diabéticas , Aldehído Reductasa , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Antioxidantes , Curcumina/farmacología , Curcumina/uso terapéutico , Diabetes Mellitus/tratamiento farmacológico , Nefropatías Diabéticas/tratamiento farmacológico , Humanos , Mediadores de Inflamación/metabolismo , Fosfatidilinositol 3-Quinasas
9.
Nutrients ; 14(9)2022 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-35565917

RESUMEN

Blood cancers are characterized by pathological disorders causing uncontrolled hematological cell division. Various strategies were previously explored for the treatment of blood cancers, including chemotherapy, Car-T therapy, targeting chimeric antigen receptors, and platelets therapy. However, all these therapies pose serious challenges that limit their use in blood cancer therapy, such as poor metabolism. Furthermore, the solubility and stability of anticancer drugs limit efficacy and bio-distribution and cause toxicity. The isolation and purification of natural killer cells during Car-T cell therapy is a major challenge. To cope with these challenges, treatment strategies from phyto-medicine scaffolds have been evaluated for blood cancer treatments. Carotenoids represent a versatile class of phytochemical that offer therapeutic efficacy in the treatment of cancer, and specifically blood cancer. Carotenoids, through various signaling pathways and mechanisms, such as the activation of AMPK, expression of autophagy biochemical markers (p62/LC3-II), activation of Keap1-Nrf2/EpRE/ARE signaaling pathway, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), increased level of reactive oxygen species, cleaved poly (ADP-ribose) polymerase (c-PARP), c-caspase-3, -7, decreased level of Bcl-xL, cycle arrest at the G0/G1 phase, and decreasing STAT3 expression results in apoptosis induction and inhibition of cancer cell proliferation. This review article focuses the therapeutic potential of carotenoids in blood cancers, addressing various mechanisms and signaling pathways that mediate their therapeutic efficacy.


Asunto(s)
Neoplasias , Receptores Quiméricos de Antígenos , Apoptosis , Carotenoides/farmacología , Carotenoides/uso terapéutico , Línea Celular Tumoral , Humanos , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , FN-kappa B/metabolismo , Neoplasias/tratamiento farmacológico , Receptores Quiméricos de Antígenos/metabolismo
10.
J Netw Comput Appl ; 1752021 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-34690484

RESUMEN

The Internet of Multimedia Things (IoMT) orchestration enables the integration of systems, software, cloud, and smart sensors into a single platform. The IoMT deals with scalar as well as multimedia data. In these networks, sensor-embedded devices and their data face numerous challenges when it comes to security. In this paper, a comprehensive review of the existing literature for IoMT is presented in the context of security and blockchain. The latest literature on all three aspects of security, i.e., authentication, privacy, and trust is provided to explore the challenges experienced by multimedia data. The convergence of blockchain and IoMT along with multimedia-enabled blockchain platforms are discussed for emerging applications. To highlight the significance of this survey, large-scale commercial projects focused on security and blockchain for multimedia applications are reviewed. The shortcomings of these projects are explored and suggestions for further improvement are provided. Based on the aforementioned discussion, we present our own case study for healthcare industry: a theoretical framework having security and blockchain as key enablers. The case study reflects the importance of security and blockchain in multimedia applications of healthcare sector. Finally, we discuss the convergence of emerging technologies with security, blockchain and IoMT to visualize the future of tomorrow's applications.

11.
IEEE Trans Industr Inform ; 17(7): 5128-5137, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33994885

RESUMEN

Industrial Internet of Things (IIoT) ensures reliable and efficient data exchanges among the industrial processes using Artificial Intelligence (AI) within the cyber-physical systems. In the IIoT ecosystem, devices of industrial applications communicate with each other with little human intervention. They need to act intelligently to safeguard the data confidentiality and devices' authenticity. The ability to gather, process, and store real-time data depends on the quality of data, network connectivity, and processing capabilities of these devices. Pervasive Edge Computing (PEC) is gaining popularity nowadays due to the resource limitations imposed on the sensor-embedded IIoT devices. PEC processes the gathered data at the network edge to reduce the response time for these devices. However, PEC faces numerous research challenges in terms of secured communication, network connectivity, and resource utilization of the edge servers. To address these challenges, we propose a secured and intelligent communication scheme for PEC in an IIoT-enabled infrastructure. In the proposed scheme, forged identities of adversaries, i.e., Sybil devices, are detected by IIoT devices and shared with edge servers to prevent upstream transmission of their malicious data. Upon Sybil attack detection, each edge server executes a parallel Artificial Bee Colony (pABC) algorithm to perform optimal network configuration of IIoT devices. Each edge server performs the job migration to their neighboring servers for load balancing and better network performance, based on their processing and storage capabilities. The experimental results justify the efficiency of our proposed scheme in terms of Sybil attack detection, the convergence curves of our pABC algorithm, delay, throughput, and control overhead of data communication using PEC for IIoT.

12.
IEEE Trans Industr Inform ; 17(8): 5829-5839, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-33981186

RESUMEN

Industry 5.0 is the digitalization, automation and data exchange of industrial processes that involve artificial intelligence, Industrial Internet of Things (IIoT), and Industrial Cyber-Physical Systems (I-CPS). In healthcare, I-CPS enables the intelligent wearable devices to gather data from the real-world and transmit to the virtual world for decision-making. I-CPS makes our lives comfortable with the emergence of innovative healthcare applications. Similar to any other IIoT paradigm, I-CPS capable healthcare applications face numerous challenging issues. The resource-constrained nature of wearable devices and their inability to support complex security mechanisms provide an ideal platform to malevolent entities for launching attacks. To preserve the privacy of wearable devices and their data in an I-CPS environment, we propose a lightweight mutual authentication scheme. Our scheme is based on client-server interaction model that uses symmetric encryption for establishing secured sessions among the communicating entities. After mutual authentication, the privacy risk associated with a patient data is predicted using an AI-enabled Hidden Markov Model (HMM). We analyzed the robustness and security of our scheme using BurrowsAbadiNeedham (BAN) logic. This analysis shows that the use of lightweight security primitives for the exchange of session keys makes the proposed scheme highly resilient in terms of security, efficiency, and robustness. Finally, the proposed scheme incurs nominal overhead in terms of processing, communication and storage and is capable to combat a wide range of adversarial threats.

13.
Crit Rev Food Sci Nutr ; 61(10): 1616-1639, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-32478608

RESUMEN

Irrespective of sex and age, cancer is the leading cause of mortality around the globe. Therapeutic incompliance, unwanted effects, and economic burdens imparted by cancer treatments, are primary health challenges. The heritable features in gene expression that are propagated through cell division and contribute to cellular identity without a change in DNA sequence are considered epigenetic characteristics and agents that could interfere with these features and are regarded as potential therapeutic targets. The genetic modification accounts for the recurrence and uncontrolled changes in the physiology of cancer cells. This review focuses on plant-derived flavonoids as a therapeutic tool for cancer, attributed to their ability for epigenetic regulation of cancer pathogenesis. The epigenetic mechanisms of various classes of flavonoids including flavonols, flavones, isoflavones, flavanones, flavan-3-ols, and anthocyanidins, such as cyanidin, delphinidin, and pelargonidin, are discussed. The outstanding results of preclinical studies encourage researchers to design several clinical trials on various flavonoids to ascertain their clinical strength in the treatment of different cancers. The results of such studies will define the clinical fate of these agents in future.


Asunto(s)
Flavonoides , Neoplasias , Dieta , Epigénesis Genética , Flavonoles , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/genética
14.
Curr Pharm Des ; 27(2): 250-262, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33234093

RESUMEN

BACKGROUND: Due to higher failure rates, lengthy time and high cost of the traditional de novo drug discovery and development process, the rate of opportunity to get new, safe and efficacious drugs for the targeted population, including pediatric patients with cancer, becomes sluggish. OBJECTIVES: This paper discusses the development of novel anticancer drugs focusing on the identification and selection of targeted anticancer drug development for the targeted population. METHODS: Information presented in this review was obtained from different databases, including PUBMED, SCOPUS, Web of Science, and EMBASE. Various keywords were used as search terms. RESULTS: The pharmaceutical companies currently are executing drug repurposing as an alternative means to accelerate the drug development process that reduces the risk of failure, time and cost, which take 3-12 years with almost 25% overall probability of success as compared to de novo drug discovery and development process (10- 17 years) which has less than 10% probability of success. An alternative strategy to the traditional de novo drug discovery and development process, called drug repurposing, is also presented. CONCLUSION: Therefore, to continue with the progress of developing novel anticancer drugs for the targeted population, identification and selection of target to specific disease type is important. Considering the aspects of the age of the patient and the disease stages such as each cancer types are different when we study the disease at a molecular level. Drug repurposing technique becomes an influential alternative strategy to discover and develop novel anticancer drug candidates.


Asunto(s)
Antineoplásicos , Neoplasias , Antineoplásicos/uso terapéutico , Niño , Descubrimiento de Drogas , Reposicionamiento de Medicamentos , Humanos , Neoplasias/tratamiento farmacológico
15.
IEEE Trans Green Commun Netw ; 5(3): 1202-1211, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35449692

RESUMEN

Internet of Things (IoT) is considered as a key enabler of health informatics. IoT-enabled devices are used for in-hospital and in-home patient monitoring to collect and transfer biomedical data pertaining to blood pressure, electrocardiography (ECG), blood sugar levels, body temperature, etc. Among these devices, wearables have found their presence in a wide range of healthcare applications. These devices generate data in real-time and transmit them to nearby gateways and remote servers for processing and visualization. The data transmitted by these devices are vulnerable to a range of adversarial threats, and as such, privacy and integrity need to be preserved. In this paper, we present LightIoT, a lightweight and secure communication approach for data exchanged among the devices of a healthcare infrastructure. LightIoT operates in three phases: initialization, pairing, and authentication. These phases ensure the reliable transmission of data by establishing secure sessions among the communicating entities (wearables, gateways and a remote server). Statistical results exhibit that our scheme is lightweight, robust, and resilient against a wide range of adversarial attacks and incurs much lower computational and communication overhead for the transmitted data in the presence of existing approaches.

16.
Ageing Res Rev ; 63: 101140, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32795505

RESUMEN

Tooth compartments and associated supportive tissues exhibit significant alterations during aging, leading to their impaired functioning. Aging not only affects the structure and function of dental tissue but also reduces its capacity to maintain physiological homeostasis and the healing process. Decreased cementocyte viability; diminished regenerative potential of stem cells residing in the pulp, alveolar bone and periodontal ligament; and impaired osteogenic and odontogenic differentiation capacity of progenitor cells are among the cellular impacts associated with oral aging. Various physiological and pathological phenomena are regulated by the epigenome, and hence, changes in epigenetic markers due to external stimuli have been reported in aging oral tissues and are considered a possible molecular mechanism underlying dental aging. The role of nutri-epigenetics in aging has emerged as an attractive research area. Thus far, various nutrients and bioactive compounds have been identified to have a modulatory effect on the epigenetic machinery, showing a promising response in dental aging. The human microbiota is another key player in aging and can be a target for anti-aging interventions in dental tissue. Considering the reversible characteristics of epigenetic markers and the potential for environmental factors to manipulate the epigenome, to minimize the deteriorative effects of aging, it is important to evaluate the linkage between external stimuli and their effects in terms of age-related epigenetic modifications.


Asunto(s)
Ligamento Periodontal , Células Madre , Envejecimiento/genética , Epigénesis Genética , Humanos , Osteogénesis
17.
Ecotoxicol Environ Saf ; 201: 110802, 2020 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-32531573

RESUMEN

Extended exposure to inorganic arsenic through contaminated drinking water has been linked with increased incidence of diabetes mellitus. The most common exposure occurs through the consumption of contaminated drinking water mainly through geogenic sources of inorganic arsenic. Epigenetic modifications are important mechanisms through which environmental pollutants could exert their toxic effects. Bisulfite sequencing polymerase chain reaction method followed by Sanger sequencing was performed for DNA methylation analysis. Our results showed that sodium arsenite treatment significantly reduced insulin secretion in pancreatic islets. It was revealed that the methylation of glucose transporter 2 (Glut2) gene was changed at two cytosine-phosphate-guanine (CpG) sites (-1743, -1734) in the promoter region of the sodium arsenite-treated group comparing to the control. No changes were observed in the methylation status of peroxisome proliferator-activated receptor-gamma (PPARγ), pancreatic and duodenal homeobox 1 (Pdx1) and insulin 2 (Ins2) CpG sites in the targeted regions. Measuring the gene expression level showed increase in Glut2 expression, while the expression of insulin (INS) and Pdx1 were significantly affected by sodium arsenite treatment. This study revealed that exposure to sodium arsenite changed the DNA methylation pattern of Glut2, a key transporter of glucose entry into the pancreatic beta cells (ß-cells). Our data suggested possible epigenetic-mediated toxicity mechanism for arsenite-induced ß-cells dysfunction. Further studies are needed to dissect the precise epigenetic modulatory activity of sodium arsenite that affect the biogenesis of insulin.


Asunto(s)
Arsenitos/toxicidad , Metilación de ADN/efectos de los fármacos , Transportador de Glucosa de Tipo 2/genética , Insulina/metabolismo , Islotes Pancreáticos/efectos de los fármacos , Compuestos de Sodio/toxicidad , Contaminantes Químicos del Agua/toxicidad , Animales , Epigénesis Genética/efectos de los fármacos , Proteínas de Homeodominio/genética , Técnicas In Vitro , Insulina/genética , Células Secretoras de Insulina/efectos de los fármacos , Células Secretoras de Insulina/metabolismo , Islotes Pancreáticos/metabolismo , Masculino , Regiones Promotoras Genéticas , Ratas , Ratas Wistar , Transactivadores/genética
18.
Life Sci ; 256: 117969, 2020 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-32553926

RESUMEN

AIMS: Cannabinoids are the chemical compounds with a high affinity for cannabinoid receptors affecting the central nervous system through the release of neurotransmitters. However, the current knowledge related to the role of such compounds in the regulation of cellular aging is limited. This study aimed to investigate the effect of cannabidiol and tetrahydrocannabinol on the function of aged pancreatic islets. MAIN METHODS: The expression of p53, p38, p21, p16, and Glut2 genes and ß-galactosidase activity were measured as hallmarks of cell aging applying real-time PCR, ELISA, and immunocytochemistry techniques. Pdx1 protein expression, insulin release, and oxidative stress markers were compared between young and aged rat pancreatic islet cells. KEY FINDINGS: Upon the treatment of aged pancreatic islets cells with cannabidiol and tetrahydrocannabinol, the expression of p53, p38, p21 and the activity of ß-galactosidase were reduced. Cannabidiol and tetrahydrocannabinol increase insulin release, Pdx1, Glut2, and thiol molecules expression, while the oxidative stress parameters were decreased. The enhanced expression of Pdx1 and insulin release in aged pancreatic islet cells reflects the extension of cell healthy aging due to the significant reduction of ROS. SIGNIFICANCE: This study provides evidence for the involvement of cannabidiol and tetrahydrocannabinol in the oxidation process of cellular aging.


Asunto(s)
Cannabinoides/farmacología , Senescencia Celular , Islotes Pancreáticos/citología , Especies Reactivas de Oxígeno/metabolismo , Animales , Biomarcadores/metabolismo , Cannabidiol/farmacología , Supervivencia Celular/efectos de los fármacos , Senescencia Celular/efectos de los fármacos , Dronabinol/farmacología , Proteínas de Homeodominio/metabolismo , Secreción de Insulina/efectos de los fármacos , Masculino , Estrés Oxidativo/efectos de los fármacos , Ratas Wistar , Transactivadores/metabolismo
19.
Environ Sci Pollut Res Int ; 27(36): 44673-44700, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32424756

RESUMEN

Ochratoxin A (OTA) is a naturally occurring mycotoxin mostly found in food items including grains and coffee beans. It induces DNA single-strand breaks and has been considered to be carcinogenic. It is recognized as a serious threat to reproductive health both in males and females. OTA is highly nephrotoxic and carcinogenic, and its potency changes evidently between species and sexes. There is a close association between OTA, mutagenicity, carcinogenicity, and genotoxicity, but the underlying mechanisms are not clear. Reports regarding genotoxic effects in relation to OTA which leads to the induction of DNA adduct formation, protein synthesis inhibition, perturbation of cellular energy production, initiation of oxidative stress, induction of apoptosis, influences on mitosis, induction of cell cycle arrest, and interference with cytokine pathways. All these mechanisms are associated with nephrotoxicity, hepatotoxicity, teratotoxicity, immunological toxicity, and neurotoxicity. OTA administration activates various mechanisms such as p38 MAPK, JNKs, and ERKs dysfunctions, BDNF disruption, TH overexpression, caspase-3 and 9 activation, and ERK-1/2 phosphorylation which ultimately lead to Alzheimer disease (AD) progression. The current review will focus on OTA in terms of recent discoveries in the field of molecular biology. The main aim is to investigate the underlying mechanisms of OTA in regard to genotoxicity and epigenetic modulations that lead to AD. Also, we will highlight the strategies for the purpose of attenuating the hazards posed by OTA exposure.


Asunto(s)
Enfermedad de Alzheimer , Ocratoxinas , Enfermedad de Alzheimer/inducido químicamente , Enfermedad de Alzheimer/genética , Daño del ADN , Epigénesis Genética , Femenino , Humanos , Masculino
20.
Biomed Pharmacother ; 130: 110714, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34321158

RESUMEN

Numerous epidemiological and clinical studies demonstrate the beneficial effects of naturally occurring, polyphenol supplementations, on cardiovascular system. The present review emphasizes on the risk factors associated with cardiovascular disorders (involving heart and blood vessels), and overview of preclinical and clinical trials on polyphenols for the treatment of cardiovascular diseases. The review collaborates PUBMED, Google Scholar and Research gate databases, which were explored using keywords and their combinations such as polyphenols, cardiovascular disease, flavonoids, atherosclerosis, cardiovascular risk factors and several others, to create an eclectic manuscript. The potency and efficacy of these polyphenols are mainly depending upon the amount of consumption and bioavailability. Recent data showed that polyphenols also exert beneficial actions on vascular system by blocking platelet aggregation and oxidation of low-density lipoprotein (LDL), ameliorating endothelial dysfunction, reducing blood pressure, improving antioxidant defenses and alleviating inflammatory responses. Several studies evidently support the cardioprotective actions mediated by polyphenols, however, some studies or long-term follow-up of human studies, did not demonstrate decisive outcomes because of variations in dose regimen and lack of appropriate controls. Therefore, more data is required to explore the therapeutic benefits of bioactive compounds as a preventive therapy for CVDs.


Asunto(s)
Sistema Cardiovascular/efectos de los fármacos , Polifenoles/farmacología , Animales , Biomarcadores , Plaquetas/efectos de los fármacos , Plaquetas/metabolismo , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/metabolismo , Manejo de la Enfermedad , Susceptibilidad a Enfermedades , Humanos , Oxidación-Reducción/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Agregación Plaquetaria/efectos de los fármacos , Factores de Riesgo
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