RESUMEN
Spinocerebellar ataxia (SCA) is a rare neurological illness inherited dominantly that causes severe impairment and premature mortality. While each rare disease may affect individuals infrequently, collectively they pose a significant healthcare challenge. It is mainly carried out due to the expansion of RNA triplet (CAG) repeats, although missense or point mutations can also be induced. Unfortunately, there is no cure; only symptomatic treatments are available. To date, SCA has about 48 subtypes, the most common of these being SCA 1, 2, 3, 6, 7, 12, and 17 having CAG repeats. Using molecular docking and molecular dynamics (MD) simulation, this study seeks to investigate effective natural herbal neuroprotective compounds against CAG repeats, which are therapeutically significant in treating SCA. Initially, virtual screening followed by molecular docking was used to estimate the binding affinity of neuroprotective natural compounds toward CAG repeats. The compound with the highest binding affinity, somniferine, was then chosen for MD simulation. The structural stability, interaction mechanism, and conformational dynamics of CAG repeats and somniferine were investigated via MD simulation. The MD study revealed that during the simulation period, the interaction between CAG repeats and somniferine stabilizes and results in fewer conformational variations. This in silico study suggests that Somniferine can be used as a therapeutic medication against RNA CAG repeats in SCA.
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Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Humanos , Descubrimiento de Drogas/métodos , ARN/química , ARN/metabolismo , Ataxias Espinocerebelosas/genética , Ataxias Espinocerebelosas/tratamiento farmacológico , Ataxias Espinocerebelosas/metabolismo , Expansión de Repetición de Trinucleótido , Repeticiones de Trinucleótidos , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/químicaRESUMEN
Spontaneous formation of a supramolecular metal-organic hydrogel using unsubstituted guanosine as a ligand and Zn2+ ions is reported. Guanosine, in the presence of NaOH, self-assembled into a stable G-quadruplex structure, which underwent crosslinking through Zn2+ ions to afford a stable hydrogel. The gel has been characterized using several spectroscopic as well as microscopic studies. The hydrogel demonstrated excellent stimuli responsiveness towards various chemicals and pH. Furthermore, the gel exhibited intrinsic thixotropic behavior and showed self-healing and injectable properties. The optical properties of the Zn-guanosine metallo-hydrogel suggested a semiconducting nature of the gel, which has been exploited for fabricating a thin film device based on a Schottky diode interface between metal and a semiconductor. The fabricated device shows excellent charge transport characteristics and linear rectifying behavior. The findings are likely to pave the way for newer research in the area of soft electronic devices fabricated using materials synthesized by employing simple biomolecules.
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The Huisgen cycloaddition, often referred to as 1,3-Dipolar cycloaddition, is a well-established method for synthesizing 1,4-disubstituted triazoles. Originally conducted under thermal conditions [3+2] cycloaddition reactions were limited by temperature, prolonged reaction time, and regioselectivity. The introduction of copper catalyzed azide-alkyne cycloaddition (CuAAC) revitalized interest, giving rise to the concept of "click chemistry". The CuAAC has emerged as a prominent method for producing 1,2,3-triazole with excellent yields and exceptional regioselectivity even in unfavorable conditions. Copper catalysts conventionally facilitate azide-alkyne cycloadditions, but challenges include instability and recycling issues. In recent years, there has been a growing demand for heterogeneous and porous catalysts in various chemical reactions. Chemists have been more interested in heterogenous catalysts as a result of the difficulties in separating homogenous catalysts from reaction products. These catalysts are favored for their abundant active sites, extensive surface area, easy separation from reaction mixtures, and the ability to be reused. Heterogeneous catalysts have garnered significant attention due to their broad industrial utility, characterized by cost-effectiveness, stability, resistance to thermal degradation, and ease of removal compared to their homogeneous counterparts. The present review covers recent advancements from year 2018 to 2023 in the field of click reactions for obtaining 1,2,3-triazoles through Cu catalyzed 1,3-dipolar azide-alkyne cycloaddition and the properties of the catalyst, reaction conditions such as solvent, temperature, reaction time, and the impact of different heterogeneous copper catalysts on product yield.
Asunto(s)
Alquinos , Azidas , Cobre , Reacción de Cicloadición , Triazoles , Cobre/química , Triazoles/química , Triazoles/síntesis química , Azidas/química , Alquinos/química , Catálisis , Estructura Molecular , Química ClicRESUMEN
The G-protein-coupled estrogen receptor-1 (GPER) is an extranuclear estrogen receptor that regulates the expression of several downstream signaling pathways with a variety of biological actions including cell migration, proliferation, and apoptosis in different parts of the brain area. It is endogenously activated by estrogen, a steroidal hormone that binds to GPER receptors which help in maintaining cellular homeostasis and neuronal integrity as well as influences neurogenesis. In contrast, neurodegenerative disorders are a big problem for society, and still many people suffer from motor and cognitive impairments. Research to date reported that GPER has the potential to whittle down motor abnormalities and cognitive dysfunction by limiting the progression of neurodegenerative disorders. Although several findings suggest that GPER activation accelerated transcription of the PI3K/Akt/Gsk-3ß and ERK1/2 signaling pathway that halt disease progression by decreasing oxidative stress, neuroinflammation, and apoptosis. Accordingly, the goal of this review is to highlight the basic mechanism of GPER signaling pathway-mediated neuroprotection in various neurodegenerative disorders including Parkinson's disease (PD), Huntington's disease (HD), Tardive dyskinesia (TD), and Epilepsy. This review also discusses the role of the GPER activators which might be a promising therapeutic target option to treat neurodegenerative disorders. All the data were obtained from published articles in PubMed (353), Web of Science (788), and Scopus (770) databases using the search terms: GPER, PD, HD, TD, epilepsy, and neurodegenerative disorders.
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Enfermedades Neurodegenerativas , Enfermedad de Parkinson , Humanos , Receptores de Estrógenos/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Transducción de Señal , Receptores Acoplados a Proteínas G/metabolismo , Proteínas de Unión al GTP/metabolismoRESUMEN
Animal models are used to better understand the various mechanisms involved in the pathogenesis of diseases and explore potential pathways that will aid in discovering therapeutic targets. 3-Nitropropionic Acid (3-NPA) is a neurotoxin used to induce Huntington's disease (HD)-like symptoms in experimental animals. The 3-NPA is a fungus toxin that impairs the complex II (succinate dehydrogenase) activity of the mitochondria and reduces ATP synthesis, leading to excessive production of free radicals resulting in the degeneration of GABAergic medium spiny neurons (MSNs) in the striatum. This is characterized by motor impairments a key clinical manifestation of HD. 3-NPA has the potential to alter several cellular processes, including mitochondrial functions, oxidative stress, apoptosis, and neuroinflammation mimicking HD-like pathogenic conditions in animals. This review strives to provide a new insight towards the 3-NPA induced molecular dysfunctioning in developing an animal model of HD. Moreover, we summarise several preclinical studies that support the use of the 3-NPA-induced models for drug discovery and development in HD. This review is a collection of various articles that were published from 1977 to 2022 on Pubmed (1639), Web of Science (2139), and Scopus (2681), which are related to the 3-NPA induced animal model.
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Enfermedad de Huntington , Animales , Enfermedad de Huntington/inducido químicamente , Enfermedad de Huntington/metabolismo , Neurotoxinas/toxicidad , Modelos Animales de Enfermedad , Nitrocompuestos/toxicidad , Propionatos/toxicidad , Descubrimiento de DrogasRESUMEN
Self-assembled metal-ion cross-linked multifunctional hydrogels are gaining a lot of attention in the fields of biomedical and biocatalysis. Herein, we report a heat-triggered metallogel that was spontaneously formed by the self-assembly of adenosine 5'-monophosphate (AMP) and cobalt chloride, accompanied by a color transition depicting an octahedral to tetrahedral transition at high temperature. The hydrogel shows excellent stability in a wide pH window from 1 to 12. The metallogel is being exploited as a multienzyme mimic, exhibiting pH-responsive catalase and peroxidase activity. Whereas catalase mimicking activity was demonstrated by the hydrogel under neutral and basic conditions, it shows peroxidase mimicking activity in an acidic medium. The multifunctionality of the synthesized metallogel was further demonstrated by phenoxazinone synthase-like activities. Owing to its catalase-mimicking activity, the metallogel could effectively reduce the oxidative stress produced in cells due to excess hydrogen peroxide by degrading H2O2 to O2 and H2O under physiological conditions. The biocompatible metallogel could prevent cell apoptosis by scavenging reactive oxygen species. A green and simple synthetic strategy utilizing commonly available biomolecules makes this metallogel highly attractive for catalytic and biomedical applications.
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Hidrogeles , Peróxido de Hidrógeno , Catalasa , Cobalto , Concentración de Iones de HidrógenoRESUMEN
A 22-year-old female presented with unexplained, non-specific, constitutional symptoms of fever, chills, rigors, and headaches of more than two-week duration. An extensive workup was done that included labs, imaging, and a liver biopsy. On examination, lymphadenopathy was found, with worsening transaminitis on labs. She was ultimately found to be hepatitis E positive. The disease was self-limited with subsidence of all symptoms with only symptomatic treatment. Hepatitis E virus infection can be a missed diagnosis as it is not common in the United States. An indicated differential diagnosis can save an extensive workup and prevent delayed diagnosis for a patient.
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Pseudotumor deltoideus refers to focal cortical irregularity and thickening at the deltoid insertion. It is benign in nature with a possible role as a tumor stimulator and possesses various anatomic variations. A well-defined area of cortical irregularity and radiological lucency at the deltoid insertion are uncommon radiological findings that pose a diagnostic dilemma. In this case report, we demonstrate a 45-year-old male with right shoulder pain along with radiological images indicative of the condition to make this previously less discussed entity more understandable. Cases of shoulder pain along with X-ray findings of cortical thickening in the proximal humerus should be investigated further with computed tomography (CT)/magnetic resonance imaging (MRI). Findings of an elongated lucency on CT and T2 hyperintensity in the cortex should help in the correct diagnosis of the condition. It should not be misdiagnosed as infective foci or a malignant entity and biopsy should be avoided.