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Neurodegeneration, the decline of nerve cells in the brain, is a common feature of neurodegenerative disorders (NDDs). Oxidative stress, a key factor in NDDs such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease can lead to neuronal cell death, mitochondria impairment, excitotoxicity, and Ca2+ stress. Environmental factors compromising stress response lead to cell damage, necessitating novel therapeutics for preventing or treating brain disorders in older individuals and an aging population. Synthetic medications offer symptomatic benefits but can have adverse effects. This research explores the potential of flavonoids derived from plants in treating NDDs. Flavonoids compounds, have been studied for their potential to enter the brain and treat NDDs. These compounds have diverse biological effects and are currently being explored for their potential in the treatment of central nervous system disorders. Flavonoids have various beneficial effects, including antiviral, anti-allergic, antiplatelet, anti-inflammatory, anti-tumor, anti-apoptotic, and antioxidant properties. Their potential to alleviate symptoms of NDDs is significant.
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Flavonoides , Enfermedades Neurodegenerativas , Flavonoides/uso terapéutico , Flavonoides/farmacología , Humanos , Enfermedades Neurodegenerativas/tratamiento farmacológico , Animales , Fármacos Neuroprotectores/uso terapéutico , Fármacos Neuroprotectores/farmacología , Estrés Oxidativo/efectos de los fármacos , Antioxidantes/uso terapéutico , Antioxidantes/farmacologíaRESUMEN
Neurodegeneration, which manifests as several chronic and incurable diseases, is an age-related condition that affects the central nervous system (CNS) and poses a significant threat to the public's health for the elderly. Recent decades have experienced an alarming increase in the incidence of neurodegenerative disorders (NDDs), a severe public health issue due to the ongoing development of people living in modern civilizations. Alzheimer's disease (AD) is a leading trigger of age-related dementia. Currently, there are no efficient therapeutics to delay, stop, or reverse the disease's course development. Several studies found that dietary bioactive phytochemicals, primarily flavonoids, influence the pathophysiological processes underlying AD. Flavonoids work well as a supplement to manufactured therapies for NDDs. Flavonoids are effective in complementing synthetic approaches to treat NDDs. They are biologically active phytochemicals with promising pharmacological activities, for instance, antiviral, anti-allergic, antiplatelet, anti-inflammatory, antitumor, anti-apoptotic, and antioxidant effects. The production of nitric oxide (NO), tumor necrosis factor (TNF-α), and oxidative stress (OS) are downregulated by flavonoids, which slow the course of AD. Hence, this research turned from preclinical evidence to feasible clinical applications to develop newer therapeutics, focusing on the therapeutic potential of flavonoids against AD.
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Pyrrole, with its versatile heterocyclic ring structure, serves as a valuable template for generating a diverse range of lead compounds with various pharmacophores. Researchers and scientists globally are intrigued by pyrrole and its analogs for their broad pharmacological potential, prompting thorough investigations aimed at advancing human welfare. This comprehensive review delves into the diverse activities exhibited by pyrrole compounds, encompassing their synthesis, reactions, and pharmacological properties alongside their derivatives. In addition to detailing the characteristics of pyrrole and its derivatives within the context of green chemistry, the review also examines microwave-assisted reactions. It provides insights into their chemical structures, natural occurrences, and potential applications across various domains. Furthermore, the article investigates structural alterations of pyrrole compounds and their implications on their functionality, highlighting their versatility as foundational elements for both functional materials and bioactive compounds. The review emphasizes the need for ongoing research and development in the field of pyrrole compounds to discover new activities and benefits.
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Pirroles , Pirroles/química , Pirroles/farmacología , Pirroles/síntesis química , Humanos , Estructura Molecular , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Microondas , Relación Estructura-Actividad , Tecnología Química VerdeRESUMEN
Coronavirus disease 2019 (COVID-19), an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been declared a global pandemic by the World Health Organization, and the situation worsens daily, associated with acute increases in case fatality rates. The main protease (Mpro) enzyme produced by SARS-CoV-2 was recently demonstrated to be responsible for not only viral reproduction but also impeding host immune responses. The element selenium (Se) plays a vital role in immune functions, both directly and indirectly. Thus, we hypothesised that Se-containing heterocyclic compounds might curb the activity of SARS-CoV-2 Mpro. We performed a molecular docking analysis and found that several of the selected selenocompounds showed potential binding affinities for SARS-CoV-2 Mpro, especially ethaselen (49), which exhibited a docking score of -6.7 kcal/mol compared with the -6.5 kcal/mol score for GC376 (positive control). Drug-likeness calculations suggested that these compounds are biologically active and possess the characteristics of ideal drug candidates. Based on the binding affinity and drug-likeness results, we selected the 16 most effective selenocompounds as potential anti-COVID-19 drug candidates. We also validated the structural integrity and stability of the drug candidate through molecular dynamics simulation. Using further in vitro and in vivo experiments, we believe that the targeted compound identified in this study (ethaselen) could pave the way for the development of prospective drugs to combat SARS-CoV-2 infections and trigger specific host immune responses.
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Antivirales/farmacología , Proteasas 3C de Coronavirus/antagonistas & inhibidores , Compuestos Heterocíclicos/farmacología , Inhibidores de Proteasas/farmacología , Selenio/análisis , Antivirales/química , Biología Computacional , Simulación por Computador , Proteasas 3C de Coronavirus/química , Compuestos Heterocíclicos/química , Humanos , Ligandos , Modelos Moleculares , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Inhibidores de Proteasas/química , Estructura Terciaria de Proteína , Pirrolidinas/química , Pirrolidinas/farmacología , Reproducibilidad de los Resultados , Ácidos SulfónicosRESUMEN
The new coronavirus (SARS-CoV-2) halts the world economy and caused unbearable medical emergency due to high transmission rate and also no effective vaccine and drugs has been developed which brought the world pandemic situations. The main protease (Mpro) of SARS-CoV-2 may act as an effective target for drug development due to the conservation level. Herein, we have employed a rigorous literature review pipeline to enlist 3063 compounds from more than 200 plants from the Asian region. Therefore, the virtual screening procedure helps us to shortlist the total compounds into 19 based on their better binding energy. Moreover, the Prime MM-GBSA procedure screened the compound dataset further where curcumin, gartanin and robinetin had a score of (-59.439, -52.421 and - 47.544) kcal/mol, respectively. The top three ligands based on binding energy and MM-GBSA scores have most of the binding in the catalytic groove Cys145, His41, Met165, required for the target protein inhibition. The molecular dynamics simulation study confirms the docked complex rigidity and stability by exploring root mean square deviations, root mean square fluctuations, solvent accessible surface area, radius of gyration and hydrogen bond analysis from simulation trajectories. The post-molecular dynamics analysis also confirms the interactions of the curcumin, gartanin and robinetin in the similar binding pockets. Our computational drug designing approach may contribute to the development of drugs against SARS-CoV-2.
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COVID-19/virología , Plantas/química , Inhibidores de Proteasas/metabolismo , SARS-CoV-2/enzimología , Humanos , Simulación de Dinámica MolecularRESUMEN
Cytokines are a protein family comprising interleukins, lymphokines, chemokines, monokines and interferons. They are significant constituents of the immune system, and they act in accordance with specific cytokine inhibiting compounds and receptors for the regulation of immune responses. Cytokine studies have resulted in the establishment of newer therapies which are being utilized for the treatment of several malignant diseases. The advancement of these therapies has occurred from two distinct strategies. The first strategy involves administrating the recombinant and purified cytokines, and the second strategy involves administrating the therapeutics which inhibits harmful effects of endogenous and overexpressed cytokines. Colony stimulating factors and interferons are two exemplary therapeutics of cytokines. An important effect of cytokine receptor antagonist is that they can serve as anti-inflammatory agents by altering the treatments of inflammation disorder, therefore inhibiting the effects of tumour necrosis factor. In this article, we have highlighted the research behind the establishment of cytokines as therapeutics and vaccine adjuvants, their role of immunotolerance, and their limitations.
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Adyuvantes de Vacunas , Citocinas , Citocinas/metabolismo , Interferones/fisiología , Factores Inmunológicos , Interleucinas/fisiología , InmunoterapiaRESUMEN
Fruits contain enormous source of vitamins that provides energy to the human body. These are also affluent in essential and vital vitamins, minerals, fiber, and health-promoting components, which has led to an increase in fruit consumption in recent years. Though fruit consumption has expanded considerably in recent years, the use of synthetic chemicals to ripen or store fruits has been steadily increasing, resulting in postharvest deterioration. Alternatives to synthetic chemicals should be considered to control this problem. Instead of utilizing synthetic chemicals, this study suggests using natural plant products to control postharvest decay. The aim of this study indicates how natural plant products can be useful and effective to eliminate postharvest diseases rather than using synthetic chemicals. Several electronic databases were investigated as information sources, including Google Scholar, PubMed, Web of Science, Scopus, ScienceDirect, SpringerLink, Semantic Scholar, MEDLINE, and CNKI Scholar. The current review focused on the postharvest of fruits has become more and more necessary because of these vast demands of fruits. Pathogen-induced diseases are the main component and so the vast portion of fruits get wasted after harvest. Besides, it may occur harmful during harvesting and subsequent handling, storage, and marketing and after consumer purchasing and also causes for numerous endogenous and exogenous diseases via activating ROS, oxidative stress, lipid peroxidation, etc. However, pathogenicity can be halted by using postharvest originating natural fruits containing bioactive elements that may be responsible for the management of nutritional deficiency, inflammation, cancer, and so on. However, issues arising during the postharvest diseases must be controlled and resolved before releasing the horticultural commodities for commercialization. Therefore, the control of postharvest pathogens still depends on the use of synthetic fungicides; however, due to the problem of the development of the fungicide-resistant strains there is a good demand of public to eradicate the use of pesticides with the arrival of numerous diseases that are expanded in their intensity by the specific chemical product. By using of the organic or natural products for controlling postharvest diseases of fruits has become a mandatory step to take. In addition, antimicrobial packaging may have a greater impact on long-term food security by lowering the risk of pathogenicity and increasing the longevity of fruit shelf life. Taken together, natural chemicals as acetaldehyde, hexanal, eugenol, linalool, jasmonates, glucosinolates, essential oils, and many plant bioactive are reported for combating of the postharvest illnesses and guide to way of storage of fruits in this review.
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Antiinfecciosos , Fungicidas Industriales , Humanos , Conservación de Alimentos/métodos , Frutas , VitaminasRESUMEN
Since its first description over a century ago, neurodegenerative diseases (NDDs) have impaired the lives of millions of people worldwide. As one of the major threats to human health, NDDs are characterized by progressive loss of neuronal structure and function, leading to the impaired function of the CNS. While the precise mechanisms underlying the emergence of NDDs remains elusive, association of neuroinflammation with the emergence of NDDs has been suggested. The immune system is tightly controlled to maintain homeostatic milieu and failure in doing so has been shown catastrophic. Here, we review current concepts on the cellular and molecular drivers responsible in the induction of neuroinflammation and how such event further promotes neuronal damage leading to neurodegeneration. Experimental data generated from cell culture and animal studies, gross and molecular pathologies of human CNS samples, and genome-wide association study are discussed to provide deeper insights into the mechanistic details of neuroinflammation and its roles in the emergence of NDDs.
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Enfermedades Neurodegenerativas , Animales , Humanos , Enfermedades Neurodegenerativas/genética , Enfermedades Neuroinflamatorias , Estudio de Asociación del Genoma Completo , InflamaciónRESUMEN
Despite significant progress in early detection and treatment, a few aggressive breast cancers still exhibit resistance to therapy. This study aimed to identify a therapeutic target for radioresistant breast cancer (RRbc) through a protein network from breast cancer genes and to evaluate potent phytochemicals against the identified target. Our approach includes the integration of differential expression genes from expression datasets to create a protein network and to use survival analysis to identify the crucial RRbc protein in order to discover a therapeutic target. Next, the phytochemicals sourced from brown algae were screened through molecular docking, ADME (absorption, distribution, metabolism, and excretion), molecular dynamics (MD) simulation, MM-GBSA, and quantum mechanics against the identified target. As a result of our protein network investigation, the proto-oncogene c-KIT (KIT) protein was identified as a potent radioresistant breast cancer target. Further, phytochemical screening establishes that nahocol-A1 from brown algae has high binding characteristics (-8.56 kcal/mol) against the KIT protein. Then, quantum chemical analysis of nahocol-A1 provided insights into its electronic properties favorable for protein binding. Also, MD simulation comprehends the conformational stability of the KIT-nahocol-A1 complex. Overall, our findings suggest nahocol-A1 could serve as a promising therapeutic candidate for radioresistant breast cancer.
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Neoplasias , Phaeophyceae , Simulación del Acoplamiento Molecular , Cromatografía de Gases , Simulación de Dinámica MolecularRESUMEN
The efflux systems are considered important mechanisms of bacterial resistance due to their ability to extrude various antibiotics. Several naturally occurring compounds, such as sesquiterpenes, have demonstrated antibacterial activity and the ability to inhibit efflux pumps in resistant strains. Therefore, the objective of this research was to analyze the antibacterial and inhibitory activity of the efflux systems NorA, Tet(K), MsrA, and MepA by sesquiterpenes nerolidol, farnesol, and α-bisabolol, used either individually or in liposomal nanoformulation, against multi-resistant Staphylococcus aureus strains. The methodology consisted of in vitro testing of the ability of sesquiterpenes to reduce the Minimum Inhibitory Concentration (MIC) and enhance the action of antibiotics and ethidium bromide (EtBr) in broth microdilution assays. The following strains were used: S. aureus 1199B carrying the NorA efflux pump, resistant to norfloxacin; IS-58 strain carrying Tet(K), resistant to tetracyclines; RN4220 carrying MsrA, conferring resistance to erythromycin. For the EtBr fluorescence measurement test, K2068 carrying MepA was used. It was observed the individual sesquiterpenes exhibited better antibacterial activity as well as efflux pump inhibition. Farnesol showed the lowest MIC of 16.5 µg/mL against the S. aureus RN4220 strain. Isolated nerolidol stood out for reducing the MIC of EtBr to 5 µg/mL in the 1199B strain, yielding better results than the positive control CCCP, indicating strong evidence of NorA inhibition. The liposome formulations did not show promising results, except for liposome/farnesol, which reduced the MIC of EtBr against 1199B and RN4220. Further research is needed to evaluate the mechanisms of action involved in the inhibition of resistance mechanisms by the tested compounds.
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Staphylococcus aureus Resistente a Meticilina , Sesquiterpenos , Farnesol/farmacología , Staphylococcus aureus/metabolismo , Staphylococcus aureus Resistente a Meticilina/metabolismo , Liposomas , Proteínas Asociadas a Resistencia a Múltiples Medicamentos , Antibacterianos/farmacología , Sesquiterpenos/farmacología , Etidio/farmacología , Pruebas de Sensibilidad Microbiana , Proteínas Bacterianas/metabolismoRESUMEN
Background and Objectives: PON1 is a multi-functional antioxidant protein that hydrolyzes a variety of endogenous and exogenous substrates in the human system. Growing evidence suggests that the Leu55Met and Gln192Arg substitutions alter PON1 activity and are linked with a variety of oxidative-stress-related diseases. Materials and Methods: We implemented structural modeling and molecular dynamics (MD) simulation along with essential dynamics of PON1 and molecular docking with their endogenous (n = 4) and exogenous (n = 6) substrates to gain insights into conformational changes and binding affinity in order to characterize the specific functional ramifications of PON1 variants. Results: The Leu55Met variation had a higher root mean square deviation (0.249 nm) than the wild type (0.216 nm) and Gln192Arg (0.202 nm), implying increased protein flexibility. Furthermore, the essential dynamics analysis confirms the structural change in PON1 with Leu55Met vs. Gln192Arg and wild type. Additionally, PON1 with Leu55Met causes local conformational alterations at the substrate binding site, leading to changes in binding affinity with their substrates. Conclusions: Our findings highlight the structural consequences of the variants, which would increase understanding of the role of PON1 in the pathogenesis of oxidative-stress-related diseases, as well as the management of endogenous and exogenous chemicals in the treatment of diseases.
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Arildialquilfosfatasa , Humanos , Antioxidantes/metabolismo , Arildialquilfosfatasa/genética , Arildialquilfosfatasa/química , Arildialquilfosfatasa/metabolismo , Simulación del Acoplamiento Molecular , Estrés Oxidativo/genéticaRESUMEN
Broad-spectrum antiviral agents targeting viral RNA-dependent RNA polymerase (RdRp) are expected to be a key therapeutic strategy in the ongoing coronavirus disease 2019 (COVID-19) pandemic and its future variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19. Molnupiravir is a nucleoside analog that in vivo experiments have been reported to inhibit the replication of SARS-CoV-2, the virus that causes COVID-19. Clinical trials of molnupiravir as a therapy for patients with mild-to-moderate COVID-19 also suggest its significant therapeutic efficacy in comparison to placebo. Molnupiravir is lethally mutagenic against viral RNA, but its effect on host cell DNA is being questioned. Herein, the safety concerns of molnupiravir are discussed with recent findings from published reports and clinical trials. The unchanged efficacy of molnupiravir against mutated SARS-CoV-2 variants is also highlighted. With its administration via the oral route, molnupiravir is expected to turn the tide of the COVID-19 pandemic.
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Tratamiento Farmacológico de COVID-19 , SARS-CoV-2 , Antivirales/efectos adversos , Citidina/análogos & derivados , Humanos , Hidroxilaminas , Mutágenos/farmacología , Pandemias , Preparaciones FarmacéuticasRESUMEN
Abnormalities in the mitogen-activated protein kinase (MAPK) signaling pathway are a key contributor to the carcinogenesis process and have therefore been implicated in several aspects of tumorigenesis, including cell differentiation, proliferation, invasion, angiogenesis, apoptosis, and metastasis. This pathway offers multiple molecular targets that may be modulated for anticancer activity and is of great interest for several malignancies. Polyphenols from various dietary sources have been observed to interfere with certain aspects of this pathway and consequently play a substantial role in the development and progression of cancer by suppressing cell growth, inactivating carcinogens, blocking angiogenesis, causing cell death, and changing immunity. A good number of polyphenolic compounds have shown promising outcomes in numerous pieces of research and are currently being investigated clinically to treat cancer patients. The current study concentrates on the role of the MAPK pathway in the development and metastasis of cancer, with particular emphasis on dietary polyphenolic compounds that influence the different MAPK sub-pathways to obtain an anticancer effect. This study aims to convey an overview of the various aspects of the MAPK pathway in cancer development and invasion, as well as a review of the advances achieved in the development of polyphenols to modulate the MAPK signaling pathway for better treatment of cancer.
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Proteínas Quinasas Activadas por Mitógenos , Neoplasias , Apoptosis , Carcinogénesis/metabolismo , Carcinógenos , Humanos , Sistema de Señalización de MAP Quinasas , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Neoplasias/tratamiento farmacológico , Neovascularización Patológica , Polifenoles/farmacología , Polifenoles/uso terapéutico , Transducción de Señal , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
Receptor for advanced glycation end-products (RAGE) is a multifunctional receptor binds a broad spectrum of ligands and mediates responses to cell damage and stress conditions. It also activates programs leading to acute and chronic inflammation and implicated in several pathological diseases, including cancer. In this review, we presented the non-enzymatic reaction of reducing sugar with the amino groups of proteins, lipids, and nucleic acids. This reaction initiates a complex series of rearrangements and dehydrations, and then produces a class of irreversibly cross-linked heterogeneous fluorescent moieties, termed advanced glycation end products (AGEs). There is a growing body of evidence that interaction of processes food-related AGEs with a cell surface receptor RAGE brings out the generation of oxidative stress and subsequently evokes proliferative, angiogenic and inflammatory reactions, thereby being involved in the development and progression of various types of cancers. This review is an insightful assessment of molecular mechanisms through which RAGE signaling contributes to the enhancement and survival of the tumorigenic cell. Here we summarize the procurement of individual ligands of RAGE like amphoterin, calcium-binding proteins, and resultant mediation of RAGE signaling pathway, which partially can elucidate the elevated risk of several cancers. Besides, we summarize many factors or conditions including APE1 (apurinic/apyrimidinic endonuclease 1), retinol mutations, retinoblastoma (Rb), proteinase 3 (PR3) hypoxia and so on through which RAGE signaling presents an establishment of cancerous environment. Additionally, we also reviewed some recent findings that give shreds of evidence for presenting the role of RAGE and its ligands in the advanced stage of cancers.
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Productos Finales de Glicación Avanzada , Neoplasias , Productos Finales de Glicación Avanzada/metabolismo , Humanos , Neoplasias/metabolismo , Estrés Oxidativo , Receptor para Productos Finales de Glicación Avanzada/metabolismo , Transducción de SeñalRESUMEN
Many short-lived and highly reactive oxygen species, such as superoxide anion (O2-) and hydrogen peroxide (H2O2), are toxic or can create oxidative stress in cells, a response involved in the pathogenesis of numerous diseases depending on their concentration, location, and cellular conditions. Superoxide dismutase (SOD) activities as an endogenous and exogenous cell defense mechanism include the potential use in treating various diseases, improving the potential use in treating various diseases, and improving food-stuffs preparation dietary supplements human nutrition. Published work indicates that SOD regulates oxidative stress, lipid metabolism, inflammation, and oxidation in cells. It can prevent lipid peroxidation, the oxidation of low-density lipoprotein in macrophages, lipid droplets' formation, and the adhesion of inflammatory cells into endothelial monolayers. It also expresses antioxidant effects in numerous cancer-related processes. Additionally, different forms of SOD may also augment food processing and pharmaceutical applications, exhibit anticancer, antioxidant, and anti-inflammatory effects, and prevent arterial problems by protecting the proliferation of vascular smooth muscle cells. Many investigations in this review have reported the therapeutic ability and physiological importance of SOD. Because of their antioxidative effects, SODs are of great potential in the medicinal, cosmetic, food, farming and chemical industries. This review discusses the findings of human and animal studies that support the advantages of SOD enzyme regulations to reduce the formation of oxidative stress in various ways.
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Peróxido de Hidrógeno , Superóxido Dismutasa , Animales , Antioxidantes/metabolismo , Antioxidantes/farmacología , Humanos , Peróxido de Hidrógeno/metabolismo , Peróxido de Hidrógeno/farmacología , Estrés Oxidativo , Especies Reactivas de Oxígeno/metabolismo , Superóxido Dismutasa/metabolismo , Superóxidos/metabolismo , Superóxidos/farmacologíaRESUMEN
The coronavirus disease 2019 (Covid-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an international public health crisis with devastating effects. In particular, this pandemic has further exacerbated the burden in tropical and subtropical regions of the world, where dengue fever, caused by dengue virus (DENV), is already endemic to the population. The similar clinical manifestations shared by Covid-19 and dengue fever have raised concerns, especially in dengue-endemic countries with limited resources, leading to diagnostic challenges. In addition, cross-reactivity of the immune responses in these infections is an emerging concern, as pre-existing DENV-antibodies might potentially affect Covid-19 through antibody-dependent enhancement. In this review article, we aimed to raise the issue of Covid-19 and dengue fever misdiagnosis, not only in a clinical setting but also with regards to cross-reactivity between SARS-CoV-2 and DENV antibodies. We also have discussed the potential consequences of overlapping immunological cascades between dengue and Covid-19 on disease severity and vaccine development.
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COVID-19/epidemiología , COVID-19/inmunología , Dengue/epidemiología , Dengue/inmunología , Animales , Anticuerpos Antivirales/inmunología , Acrecentamiento Dependiente de Anticuerpo/inmunología , Asia/epidemiología , COVID-19/virología , Coinfección/epidemiología , Coinfección/inmunología , Coinfección/virología , Dengue/virología , Virus del Dengue/inmunología , Virus del Dengue/patogenicidad , Humanos , Pandemias/prevención & control , SARS-CoV-2/inmunología , SARS-CoV-2/patogenicidadRESUMEN
BACKGROUND: The current study aimed to investigate the stimulatory effect of beta-adrenergic receptors (ß-ARs) on brain derived neurotropic factor (BDNF) and cAMP response element binding protein (CREB). METHODS: Human Müller cells were cultured in low and high glucose conditions. Cells were treated with xamoterol (selective agonist for ß1-AR), salmeterol (selective agonist for ß2-AR), isoproterenol (ß-ARs agonist) and propranolol (ß-ARs antagonist), at 20 µM concentration for 24 h. Western Blotting assay was performed for the gene expression analysis. DNA damage was evaluated by TUNEL assay. DCFH-DA assay was used to check the level of reactive oxygen species (ROS). Cytochrome C release was measured by ELISA. RESULTS: Xamoterol, salmeterol and isoproterenol showed no effect on Caspase-8 but it reduced the apoptosis and increased the expression of BDNF in Müller cells. A significant change in the expression of caspase-3 was observed in cells treated with xamoterol and salmeterol as compared to isoproterenol. Xamoterol, salmeterol and isoproterenol significantly decreased the reactive oxygen species (ROS) when treated for 24 hours. Glucose-induced cytochrome c release was disrupted in Müller cells. CONCLUSION: ß-ARs, stimulated by agonist play a protective role in hyperglycemic Müller cells, with the suppression of glucose-induced caspase-3 and cytochrome c release. B-Ars may directly mediate the gene expression of BDNF.
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Células Ependimogliales , Propranolol , Agonistas Adrenérgicos beta/farmacología , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Caspasa 3/metabolismo , Caspasa 8/metabolismo , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Citocromos c/metabolismo , Células Ependimogliales/metabolismo , Glucosa/farmacología , Humanos , Isoproterenol/farmacología , Propranolol/farmacología , Especies Reactivas de Oxígeno/metabolismo , Receptores Adrenérgicos beta/metabolismo , Receptores Adrenérgicos beta 2/genética , Xinafoato de Salmeterol/farmacología , Xamoterol/farmacologíaRESUMEN
Tuberculosis has become a major health problem globally. This is worsened by the emergence of resistant strains of Mycobacterium tuberculosis showing ability to evade the effectiveness of the current antimycobacterial therapies. Therefore, the efforts carried out to explore new entities from many sources, including marine, are critical. This review summarizes several marine-derived macrolides that show promising activity against M. tuberculosis. We also provide information regarding the biosynthetic processes of marine macrolides, including the challenges that are usually experienced in this process. As most of the studies reporting the antimycobacterial activities of the listed marine macrolides are based on in vitro studies, the future direction should consider expanding the trials to in vivo and clinical trials. In addition, in silico studies should also be explored for a quick screening on marine macrolides with potent activities against mycobacterial infection. To sum up, macrolides derived from marine organisms might become therapeutical options for tackling antimycobacterial resistance of M. tuberculosis.
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Mycobacterium tuberculosis , Tuberculosis , Humanos , Macrólidos/farmacología , Antituberculosos/farmacología , Antituberculosos/uso terapéutico , Farmacorresistencia Bacteriana , Tuberculosis/tratamiento farmacológico , Pruebas de Sensibilidad MicrobianaRESUMEN
Microbes in marine ecosystems are known to produce secondary metabolites. One of which are carotenoids, which have numerous industrial applications, hence their demand will continue to grow. This review highlights the recent research on natural carotenoids produced by marine microorganisms. We discuss the most recent screening approaches for discovering carotenoids, using in vitro methods such as culture-dependent and culture-independent screening, as well as in silico methods, using secondary metabolite Biosynthetic Gene Clusters (smBGCs), which involves the use of various rule-based and machine-learning-based bioinformatics tools. Following that, various carotenoids are addressed, along with their biological activities and metabolic processes involved in carotenoids biosynthesis. Finally, we cover the application of carotenoids in health and pharmaceutical industries, current carotenoids production system, and potential use of synthetic biology in carotenoids production.
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Carotenoides , Ecosistema , Carotenoides/farmacología , Biología Computacional , Familia de Multigenes , Biología SintéticaRESUMEN
This review summarized the current breakthroughs in the chemistry of acridines as anti-cancer agents, including new structural and biologically active acridine attributes. Acridine derivatives are a class of compounds that are being extensively researched as potential anti-cancer drugs. Acridines are well-known for their high cytotoxic activity; however, their clinical application is restricted or even excluded as a result of side effects. The photocytotoxicity of propyl acridine acts against leukaemia cell lines, with C1748 being a promising anti-tumour drug against UDP-UGT's. CK0403 is reported in breast cancer treatment and is more potent than CK0402 against estrogen receptor-negative HER2. Acridine platinum (Pt) complexes have shown specificity on the evaluated DNA sequences; 9-anilinoacridine core, which intercalates DNA, and a methyl triazene DNA-methylating moiety were also studied. Acridine thiourea gold and acridinone derivatives act against cell lines such as MDA-MB-231, SK-BR-3, and MCF-7. Benzimidazole acridine compounds demonstrated cytotoxic activity against Dual Topo and PARP-1. Quinacrine, thiazacridine, and azacridine are reported as anti-cancer agents, which have been reported in the previous decade and were addressed in this review article.