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1.
Chem Biol Interact ; 395: 111000, 2024 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-38614318

RESUMEN

Nucleic acid delivery by viral and non-viral methods has been a cornerstone for the contemporary gene therapy aimed at correcting the defective genes, replacing of the missing genes, or downregulating the expression of anomalous genes is highly desirable for the management of various diseases. Ostensibly, it becomes paramount for the delivery vectors to intersect the biological barriers for accessing their destined site within the cellular environment. However, the lipophilic nature of biological membranes and their potential to limit the entry of large sized, charged, hydrophilic molecules thus presenting a sizeable challenge for the cellular integration of negatively charged nucleic acids. Furthermore, the susceptibility of nucleic acids towards the degrading enzymes (nucleases) in the lysosomes present in cytoplasm is another matter of concern for their cellular and nuclear delivery. Hence, there is a pressing need for the identification and development of cationic delivery systems which encapsulate the cargo nucleic acids where the charge facilitates their cellular entry by evading the membrane barriers, and the encapsulation shields them from the enzymatic attack in cytoplasm. Cycloamylose bearing a closed loop conformation presents a robust candidature in this regard owing to its remarkable encapsulating tendency towards nucleic acids including siRNA, CpG DNA, and siRNA. The presence of numerous hydroxyl groups on the cycloamylose periphery provides sites for its chemical modification for the introduction of cationic groups, including spermine, (3-Chloro-2 hydroxypropyl) trimethylammonium chloride (Q188), and diethyl aminoethane (DEAE). The resulting cationic cycloamylose possesses a remarkable transfection efficiency and provides stability to cargo oligonucleotides against endonucleases, in addition to modulating the undesirable side effects such as unwanted immune stimulation. Cycloamylose is known to interact with the cell membranes where they release certain membrane components such as phospholipids and cholesterol thereby resulting in membrane destabilization and permeabilization. Furthermore, cycloamylose derivatives also serve as formulation excipients for improving the efficiency of other gene delivery systems. This review delves into the various vector and non-vector-based gene delivery systems, their advantages, and limitations, eventually leading to the identification of cycloamylose as an ideal candidate for nucleic acid delivery. The synthesis of cationic cycloamylose is briefly discussed in each section followed by its application for specific delivery/transfection of a particular nucleic acid.


Asunto(s)
Cationes , Ácidos Nucleicos , Ácidos Nucleicos/química , Cationes/química , Humanos , Nanopartículas/química , Portadores de Fármacos/química , Técnicas de Transferencia de Gen , Animales
2.
Biomol Ther (Seoul) ; 32(3): 390-398, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38586882

RESUMEN

FoxO1, a member of the Forkhead transcription factor family subgroup O (FoxO), is expressed in a range of cell types and is crucial for various pathophysiological processes, such as apoptosis and inflammation. While FoxO1's roles in multiple diseases have been recognized, the target has remained largely unexplored due to the absence of cost-effective and efficient inhibitors. Therefore, there is a need for natural FoxO1 inhibitors with minimal adverse effects. In this study, docking, MMGBSA, and ADMET analyses were performed to identify natural compounds that exhibit strong binding affinity to FoxO1. The top candidates were then subjected to molecular dynamics (MD) simulations. A natural product library was screened for interaction with FoxO1 (PDB ID- 3CO6) using the Glide module of the Schrödinger suite. In silico ADMET profiling was conducted using SwissADME and pkCSM web servers. Binding free energies of the selected compounds were assessed with the Prime-MMGBSA module, while the dynamics of the top hits were analyzed using the Desmond module of the Schrödinger suite. Several natural products demonstrated high docking scores with FoxO1, indicating their potential as FoxO1 inhibitors. Specifically, the docking scores of neochlorogenic acid and fraxin were both below -6.0. These compounds also exhibit favorable drug-like properties, and a 25 ns MD study revealed a stable interaction between fraxin and FoxO1. Our findings highlight the potential of various natural products, particularly fraxin, as effective FoxO1 inhibitors with strong binding affinity, dynamic stability, and suitable ADMET profiles.

3.
J Biomol Struct Dyn ; : 1-13, 2024 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-38400742

RESUMEN

Activation of NLRP3 (NOD-like receptor family, pyrin domain-containing protein 3) has been associated with multiple chronic pathologies, including diabetes, atherosclerosis, and rheumatoid arthritis. Moreover, histone deacetylases (HDACs), specifically HDAC6 is required for the NLRP3 inflammasome to assemble and activate. Thus, NLRP3 serves as an attractive target for the development of novel therapeutic approaches. Several companies are now attempting to develop specific modulators of the NLRP3 inflammasome, but only a handful of small molecules of NLRP3 inflammasome inhibitors, such as MCC950 and Tranilast, are currently available for clinical use. However, their use is limited due to severe side effects and short half-lives. Thus, the repurposing of FDA-approved drugs with NLRP3 inhibitory activity is needed. The present study was aimed at repurposing preexisting drugs that might act as safe and effective NLRP3 inhibitors. A library of 2,697 FDA-approved drugs was screened for binding with NLRP3 (PDB: 7ALV) using Glide (Schrödinger). The top seven FDA-approved drugs with potential binding affinities were selected based on docking scores and subjected to ADMET profiling using pkCSM and SwissADME. The binding of the ADMET-favorable FDA-approved drugs to NLRP3 was validated using MMGBSA (Prime) and Molecular Dynamics (Desmond) in the Schrödinger suite. ADMET profiling revealed that of the seven best docking drugs, empagliflozin and citicoline had good drug-likeness properties. Moreover, MMGBSA analysis and molecular dynamics demonstrated that empagliflozin and citicoline exhibited stable ligand-NLRP3 interactions in the presence of solvents. This study sheds light on the ability of various FDA-approved drugs to act as NLRP3 inhibitors.Communicated by Ramaswamy H. Sarma.

4.
Naunyn Schmiedebergs Arch Pharmacol ; 397(1): 281-303, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37421431

RESUMEN

Chronically stressed patients often have low vagal tone and increased levels of proinflammatory cytokines, which increase their risk for developing cardiac dysfunction. Transcutaneous vagus nerve stimulation (taVNS) is a way to activate the parasympathetic system, which has the ability to reduce inflammation and antagonize excessive sympathetic responses. However, the effectiveness of taVNS in treating cardiac dysfunction caused by chronic unpredictable stress (CUS) has not been studied. To investigate this, we first validated a rat model of CUS, in which the rats were exposed to random stressors daily for 8 weeks. Post CUS, the rats were treated with taVNS (1.0 ms, 6 V, 6 Hz, for 40 min × 2 weeks, alternatively) and their cardiac function and cholinergic flow were evaluated. Furthermore, serum cardiac troponin I (cTnI), cardiac caspase-3, inducible nitric oxide synthase (iNOS), and transforming growth factor (TGF)-ß1 expression in rats were also assessed. The chronically stressed rats showed depressed behavior with increased levels of serum corticosterone and proinflammatory cytokines. Electrocardiogram (ECG) and heart rate variability (HRV) studies revealed elevated heart rate, diminished vagal tone, and altered sinus rhythm in CUS rats. Furthermore, the CUS rats demonstrated cardiac hypertrophy and fibrosis with increased caspase-3, iNOS, and TGF-ß expression in their myocardium and increased levels of serum cTnI. Interestingly, alternate taVNS therapy for 2 weeks, post CUS, helped alleviate these cardiac abnormalities. These suggest that taVNS could be a useful adjunctive and non-pharmacological approach for managing CUS induced cardiac dysfunction.


Asunto(s)
Cardiopatías , Estimulación del Nervio Vago , Humanos , Ratas , Animales , Caspasa 3 , Nervio Vago/fisiología , Citocinas
5.
Pathol Res Pract ; 253: 155038, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38101157

RESUMEN

Lung cancer is one of the leading causes of death worldwide, whereby the major contributing factors are cigarette smoking and exposure to environmental pollutants. Despite the availability of numerous treatment options, including chemotherapy, the five-year survival rate is still extremely low, highlighting the urgent need to develop novel, more effective therapeutic strategies. In this context, the repurposing of previously approved drugs is an advantage in terms of time and resources invested. Ribavirin is an antiviral drug approved for the treatment of hepatitis C, which shows potential for repurposing as an anticancer agent. Among the many signaling molecules promoting carcinogenesis, the interleukins (ILs) IL-6 and IL-8 are interesting therapeutic targets as they promote a variety of cancer hallmarks such as cell proliferation, migration, metastasis, and angiogenesis. In the present study, we show that ribavirin significantly downregulates the expression of IL-6 and IL-8 in vitro in A549 human lung adenocarcinoma cells. The results of this study shed light on the anticancer mechanisms of ribavirin, providing further proof of its potential as a repurposed drug for the treatment of lung cancer.


Asunto(s)
Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Humanos , Ribavirina/farmacología , Ribavirina/uso terapéutico , Interleucina-6 , Interleucina-8 , Adenocarcinoma del Pulmón/tratamiento farmacológico , Neoplasias Pulmonares/patología , Carcinogénesis
6.
Int J Biol Macromol ; 259(Pt 1): 128932, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38143069

RESUMEN

With the growing demand for extending the shelf-life of perishable goods such as fruits and vegetables, there is continued interest towards the development of edible coatings derived from natural sources. To avoid rapid dissolution, water insoluble polysaccharide such as chitosan has been widely explored. In this work, we developed robust hyaluronic acid-based edible polysaccharide-protein coatings by combining it (hyaluronic acid) with chitosan and gelatin to introduce additional antioxidant properties. This work is the first example of using hyaluronic acid in edible coatings for fruit preservation. The effect of developed edible composite coatings on the quality of coated strawberries was investigated over a 15 day storage period with 3-day examination intervals. The obtained results revealed hyaluronic acid dose-dependent improvement in intrinsic properties of coated strawberries including weight loss, pH, titratable acidity (TA) and total solids content (TSS). Furthermore, the inclusion of hyaluronic acid significantly enhanced the antioxidant properties of developed edible coatings as measured using total phenolic content, change in ascorbic acid content and DPPH assay prolonging the shelf-life of coated strawberries.


Asunto(s)
Quitosano , Películas Comestibles , Fragaria , Antioxidantes/química , Fragaria/química , Conservación de Alimentos/métodos , Ácido Hialurónico , Frutas/química , Quitosano/química , Polisacáridos/química , Proteínas/análisis
7.
Int Immunopharmacol ; 125(Pt A): 111046, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37879231

RESUMEN

The global incidence of autoimmune diseases is on the rise, and many healthcare professionals believe that chronic stress plays a prominent role in both the aggravation and remission of these conditions. It is believed that prolonged exposure to stress is associated with neuroimmune axis malfunction, which eventually dysregulates multiple immunological factors as well as deregulates autoimmune responses that play a central role in various autoimmune diseases, including rheumatoid arthritis and psoriasis. Herein, we performed validation of an 8-week long rat model of chronic unpredictable stress (CUS) which consisted of exposing groups of rats to random stressors daily for 8 weeks. Additionally, we developed a novel rat model combining 8-week long random stressor-induced CUS with CIA-triggered arthritis and IMQ-triggered psoriasis and have successfully used both these models to assess the role of chronic stress in the aggravation of arthritis and psoriasis, respectively. Notably, the 8-week CUS protocol extensively aggravated and prolonged both arthritis and psoriasis condition in the rat model by upregulating the release of different pro-inflammatory cytokines, dysregulation of immune cell responses and oxidative stress system, which were all related to severe inflammation. Further, CUS aggravated macroscopic features and the increase in destruction of joint tissue and epidermal thickness induced by CIA and IMQ, respectively, in rats. In conclusion, this study suggests that exposure to an 8-week long CUS paradigm aggravates the distinctive characteristics of rheumatoid arthritis and psoriasis in rats via amplifying the inflammatory circuits and immune cell responses linked to these autoimmune diseases.


Asunto(s)
Artritis Experimental , Artritis Reumatoide , Enfermedades Autoinmunes , Psoriasis , Humanos , Ratas , Animales , Inflamación , Citocinas
8.
J Mater Sci Mater Med ; 34(10): 49, 2023 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-37796399

RESUMEN

Peripheral demyelinating diseases entail damage to axons and Schwann cells in the peripheral nervous system. Because of poor prognosis and lack of a cure, this group of diseases has a global impact. The primary underlying cause of these diseases involves the inability of Schwann cells to remyelinate the damaged insulating myelin around axons, resulting in neuronal death over time. In the past decade, extensive research has been directed in the direction of Schwann cells focusing on their physiological and neuroprotective effects on the neurons in the peripheral nervous system. One cause of dysregulation in the remyelinating function of Schwann cells has been associated with oxidative stress. Tissue-engineered biodegradable scaffolds that can stimulate remyelination response in Schwann cells have been proposed as a potential treatment strategy for peripheral demyelinating diseases. However, strategies developed to date primarily focussed on either remyelination or oxidative stress in isolation. Here, we have developed a multifunctional nanofibrous scaffold with material and biochemical cues to tackle both remyelination and oxidative stress in one matrix. We developed a nanofibrous scaffold using polycaprolactone (PCL) as a foundation loaded with antioxidant graphene oxide (GO) and coated this bioscaffold with Schwann cell acellular matrix. In vitro studies revealed both antioxidant and remyelination properties of the developed bioscaffold. Based on the results, the developed multifunctional bioscaffold approach can be a promising biomaterial approach for treating demyelinating diseases.


Asunto(s)
Enfermedades Desmielinizantes , Nanofibras , Humanos , Antioxidantes , Enfermedades Desmielinizantes/terapia
9.
Toxicol In Vitro ; 92: 105660, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37591407

RESUMEN

Airway remodelling occurs in chronic respiratory diseases (CRDs) such as asthma and chronic obstructive pulmonary disease (COPD). It is characterized by aberrant activation of epithelial reparation, excessive extracellular matrix (ECM) deposition, epithelial-to-mesenchymal transition (EMT), and airway obstruction. The master regulator is Transforming Growth Factor-ß (TGF-ß), which activates tissue repair, release of growth factors, EMT, increased cell proliferation, and reduced nitric oxide (NO) secretion. Due to its fundamental role in remodelling, TGF-ß is an emerging target in the treatment of CRDs. Berberine is a benzylisoquinoline alkaloid with antioxidant, anti-inflammatory, and anti-fibrotic activities whose clinical application is hampered by poor permeability. To overcome these limitations, in this study, berberine was encapsulated in monoolein-based liquid crystalline nanoparticles (BM-LCNs). The potential of BM-LCNs in inhibiting TGF-ß-induced remodelling features in human bronchial epithelial cells (BEAS-2B) was tested. BM-LCNs significantly inhibited TGF-ß-induced migration, reducing the levels of proteins upregulated by TGF-ß including endoglin, thrombospondin-1, basic fibroblast growth factor, vascular-endothelial growth factor, and myeloperoxidase, and increasing the levels of cystatin C, a protein whose expression was downregulated by TGF-ß. Furthermore, BM-LCNs restored baseline NO levels downregulated by TGF-ß. The results prove the in vitro therapeutic efficacy of BM-LCNs in counteracting TGF-ß-induced remodelling features. This study supports the suitability of berberine-loaded drug delivery systems to counteract airway remodelling, with potential application as a treatment strategy against CRDs.


Asunto(s)
Berberina , Humanos , Berberina/farmacología , Remodelación de las Vías Aéreas (Respiratorias) , Antioxidantes , Proliferación Celular , Células Epiteliales
10.
Metabolites ; 13(4)2023 Mar 24.
Artículo en Inglés | MEDLINE | ID: mdl-37110125

RESUMEN

Glutathione is a naturally occurring compound that plays a crucial role in the cellular response to oxidative stress through its ability to quench free radicals, thus mitigating the risk of potential damage, including cell death. While glutathione is endogenously present in different plants and animal cells, their concentration varies considerably. The alteration in glutathione homeostasis can be used as a potential marker for human diseases. In the case of the depletion of endogenous glutathione, exogenous sources can be used to replenish the pool. To this end, both natural and synthetic glutathione can be used. However, the health benefit of glutathione from natural sources derived from fruits and vegetables is still debated. There is increasingly growing evidence of the potential health benefits of glutathione in different diseases; however, the determination and in situ quantification of endogenously produced glutathione remains a major challenge. For this reason, it has been difficult to understand the bioprocessing of exogenously delivered glutathione in vivo. The development of an in situ technique will also aid in the routine monitoring of glutathione as a biomarker for different oxidative stress-mediated diseases. Furthermore, an understanding of the in vivo bioprocessing of exogenously delivered glutathione will also aid the food industry both towards improving the longevity and profile of food products and the development of glutathione delivery products for long-term societal health benefits. In this review, we surveyed the natural plant-derived sources of glutathione, the identification and quantification of extracted glutathione from these sources, and the role of glutathione in the food industry and its effect on human health.

11.
Physiol Behav ; 267: 114207, 2023 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-37100219

RESUMEN

Chronic stress is a major risk factor for various diseases, including cardiovascular diseases (CVDs). Chronic stress enhances the release of pro-inflammatory cytokines like IL-1ß, IL-6, and TNF-α, making individuals susceptible to atherosclerosis which is dominant cause for CVDs. In present study, we validated a mouse model of chronic unpredictable stress (CUS), and assessed the characteristic features of atherosclerosis in thoracic aortas of CUS mice. The CUS procedure consisted of exposing groups of mice to random stressors daily for 10-weeks. The stress response was verified by presence of depressive-like behaviors and increased serum corticosterone in mice which was determined by battery of behavioural tests (SPT, EPMT, NSFT) and ELISA, respectively. Atherosclerosis parameters in CUS mice were evaluated by lipid indices estimation followed by histological assessment of plaque deposition and fibrosis in thoracic aorta. Further, we assessed the efficacy of a polyphenol, i.e. Butein in conferring protection against chronic stress-induced atherosclerosis and the possible mechanism of action. Butein (20 mg/kg x 28 days, alternatively, i.p.) was administered to CUS mice after 6-weeks of CUS exposure till the end of the protocol. Butein treatment decreased peripheral IL-1ß and enhanced peripheral as well as central BDNF levels. Histological assessment revealed decreased macrophage expression and reduced fibrosis in thoracic aorta of Butein treated mice. Further, treatment with Butein lowered lipid indices in CUS mice. Our findings thus, suggest that 10-weeks of CUS induce characteristic features of atherosclerosis in mice and Butein can offer protection in CUS-induced atherosclerosis through multiple mechanisms including anti-inflammatory, antifibrotic and anti-adipogenic actions.


Asunto(s)
Aterosclerosis , Factor Neurotrófico Derivado del Encéfalo , Ratones , Animales , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Antiinflamatorios/uso terapéutico , Aterosclerosis/tratamiento farmacológico , Fibrosis , Lípidos , Estrés Psicológico/complicaciones
12.
RSC Adv ; 13(2): 1392-1401, 2023 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-36712918

RESUMEN

Nerve tissue engineering aims to create scaffolds that promote nerve regeneration in the damaged peripheral nervous system. However, there remain some challenges in the construction of scaffolds in terms of mechanical properties and cellular behaviour. The present work aims to develop multifunctional implantable nanofibrous scaffolds for nerve regeneration. Using electrospinning, nanofibrous neat polycaprolactone (PCL) and PCL/multiwalled carbon nanotubes (PCL-MWCNT) composite scaffolds were prepared in random and aligned morphology. Schwann cells and their secreted biochemical factors are responsible for neuronal survival in the peripheral nervous system. Therefore, the acellular matrix of Schwann cells was spin-coated on the PCL-MWCNT scaffolds to aid nerve regeneration. Physicochemical and mechanical properties, and the in vitro cellular response of the developed nanofibrous were investigated. We observed no significant change in fibre diameter between neat PCL and PCL-MWCNT scaffolds regardless of the morphology. However, the inclusion of MWCNT reduced the mechanical strength of nanocomposite scaffolds compared to neat PCL. In vitro study revealed biocompatibility of the developed scaffolds both with and without an acellular matrix. Gene expression study revealed a significant increase in peripheral myelin protein (PMP22) expression on acellular matrix-coated PCL-MWCNT scaffolds compared to neat PCL counterparts. Overall, the results suggested Schwann cell matrix-coated PCL-MWCNT nanofibers as a promising conduit for peripheral nerve regeneration.

14.
Gels ; 8(10)2022 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-36286146

RESUMEN

In the present investigation, Aloe vera gel (AVG)-based edible coatings enriched with anthocyanin were prepared. We investigated the effect of different formulations of aloe-vera-based edible coatings, such as neat AVG (T1), AVG with glycerol (T2), Aloe vera with 0.2% anthocyanin + glycerol (T3), and AVG with 0.5% anthocyanin + glycerol (T4), on the postharvest quality of fig (Ficus carica L.) fruits under refrigerated conditions (4 °C) for up to 12 days of storage with 2-day examination intervals. The results of the present study revealed that the T4 treatment was the most effective for reducing the weight loss in fig fruits throughout the storage period (~4%), followed by T3, T2, and T1. The minimum weight loss after 12 days of storage (3.76%) was recorded for the T4 treatment, followed by T3 (4.34%), which was significantly higher than that of uncoated fruit (~11%). The best quality attributes, such as the total soluble solids (TSS), titratable acidity (TA), and pH, were also demonstrated by the T3 and T4 treatments. The T4 coating caused a marginal change of 0.16 in the fruit titratable acidity, compared to the change of 0.33 in the untreated fruit control after 12 days of storage at 4 °C. Similarly, the total soluble solids in the T4-coated fruits increased marginally (0.43 °Brix) compared to the uncoated control fruits (>2 °Brix) after 12 days of storage at 4 °C. The results revealed that the incorporation of anthocyanin content into AVG is a promising technology for the development of active edible coatings to extend the shelf life of fig fruits.

15.
J Neurol Sci ; 434: 120099, 2022 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-34965490

RESUMEN

Motor neuron diseases (MNDs) are rare and frequently fatal neurological disorders in which motor neurons within the brainstem and spinal cord regions slowly die. MNDs are primarily caused by genetic mutations, and > 100 different mutant genes in humans have been discovered thus far. Given the fact that many more MND-related genes have yet to be discovered, the growing body of genetic evidence has offered new insights into the diverse cellular and molecular mechanisms involved in the aetiology and pathogenesis of MNDs. This search may aid in the selection of potential candidate genes for future investigation and, eventually, may open the door to novel interventions to slow down disease progression. In this review paper, we have summarized detailed existing research findings of different MNDs, such as amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), spinal bulbar muscle atrophy (SBMA) and hereditary spastic paraplegia (HSP) in relation to their complex genetic architecture.


Asunto(s)
Esclerosis Amiotrófica Lateral , Enfermedad de la Neurona Motora , Atrofia Muscular Espinal , Paraplejía Espástica Hereditaria , Esclerosis Amiotrófica Lateral/genética , Humanos , Enfermedad de la Neurona Motora/genética , Enfermedad de la Neurona Motora/patología , Neuronas Motoras/patología , Atrofia Muscular Espinal/genética , Paraplejía Espástica Hereditaria/genética
16.
Heliyon ; 7(12): e08522, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34917808

RESUMEN

People with chronic stress have higher levels of pro-inflammatory cytokines, which enhance their susceptibility to cardiovascular diseases. Diacerein has ability to modulate pro-inflammatory cytokines such as IL-1ß and IL-6; however, its efficacy in chronic stress associated cardiovascular diseases is not yet assessed. In this study, we standardized a rat model of chronic unpredictable stress (CUS) demonstrating cardiovascular dysfunctions and further assessed the effect of IL-6 modulator, diacerein, on cardiovascular functions in CUS exposed rats. The CUS procedure consisted of exposing male albino Wistar rats to random stressors, everyday for 8 weeks. The binding affinity of diacerein with IL-6 was ascertained using Docking tools viz AutoDock and SwissDock. Moreover, diacerein was administered (50 mg/kg/day x 20 days P.O) post CUS exposure to rats and the serum IL-6 levels and heart functions of CUS rats were determined by ELISA and ECG-HRV analysis, respectively. 8 weeks of CUS exposure resulted in two-fold increase in serum corticosterone and IL-6 levels in rats. The ECG and HRV analysis of CUS rats showed altered sinus rhythm, elevated heart rate, systolic blood pressure and sympathetic tone. Molecular docking studies revealed diacerein high binding affinity towards IL-6 receptor. The post-treatment of diacerein in CUS rats prevented these cardiovascular dysfunctions. Our findings thus suggests that IL-6 may have a prominent role in chronic stress induced cardiovascular dysfunctions and diacerein, could be used as a preventive measure for such conditions.

17.
Nanotechnology ; 32(47)2021 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-34380124

RESUMEN

There is a renewed interest in nanodiamonds and their applications in biology and medicine, especially in bioimaging and photothermal therapy. This is due to their small size, chemical inertness and unique photo-properties such as bright and robust fluorescence, resistant to photobleaching and photothermal response under near infrared (NIR) irradiation. However, the biggest challenge limiting the wide-spread use of nanodiamonds is the high-energy consuming, dangerous and sophisticated synthetic methods currently adopted by industry named higher temperature high pressure approach, and detonation method. Despite over a decade of research towards the development of new synthetic approaches, most of the methods developed to date require sophisticated instrumentations and have high energy demand. To circumvent the reliance on high energy demanding sophisticated experimental setups, here we present a simple synthetic approach using solar energy as a sustainable sole energy source. Using low-grade coal as carbon precursor, we used high power magnifying glasses to concentrate and focus sunlight to induce synthesis of nanodiamonds. The synthesized nanodiamonds exhibit similar physicochemical and photo-properties as nanodiamonds synthesized using other synthetic approaches.In vitrostudies using macrophage Raw 264.7 cells demonstrated rapid uptake and bright fluorescence of the synthesized nanodiamonds with superior biocompatibility (≥95% cell viability). The synthesized nanodiamonds also exhibited dose dependent photothermal response under NIR irradiation.


Asunto(s)
Calor , Nanodiamantes , Fototerapia , Luz Solar , Animales , Ratones , Nanodiamantes/química , Nanodiamantes/uso terapéutico , Células RAW 264.7
18.
Nanomedicine (Lond) ; 16(18): 1595-1611, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-34180261

RESUMEN

Aim: Quantum dots (QDs) are nanoparticles that have an emerging application as theranostic agents in several neurodegenerative diseases. The advantage of QDs as nanomedicine is due to their unique optical properties that provide high sensitivity, stability and selectivity at a nanoscale range. Objective: To offer renewed insight into current QD research and elucidate its promising application in Alzheimer's disease (AD) diagnosis and therapy. Methods: A comprehensive literature search was conducted in PubMed and Google Scholar databases that included the following search terms: 'quantum dots', 'blood-brain barrier', 'cytotoxicity', 'toxicity' and 'Alzheimer's disease'; PRISMA guidelines were adhered to. Results: Thirty-four publications were selected to evaluate the ability of QDs to cross the blood-brain barrier, potential toxicity and current AD diagnostic and therapeutic applications. Conclusion: QD's unique optical properties and versatility to conjugate to various biomolecules, while maintaining a nanoscale size, render them a promising theranostic tool in AD.


Asunto(s)
Enfermedad de Alzheimer , Nanopartículas , Puntos Cuánticos , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/tratamiento farmacológico , Humanos , Nanomedicina , Medicina de Precisión , Nanomedicina Teranóstica
19.
Heliyon ; 7(4): e06854, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33981903

RESUMEN

Myocyte enhancer factor 2 (MEF2), a family of transcription factor of MADS (minichromosome maintenance 1, agamous, deficiens and serum response factor)-box family needed in the growth and differentiation of a variety of human cells, such as neural, immune, endothelial, and muscles. As per existing literature, MEF2 transcription factors have also been associated with synaptic plasticity, the developmental mechanisms governing memory and learning, and several neurologic conditions, like autism spectrum disorders (ASDs). Recent genomic findings have ascertained a link between MEF2 defects, particularly in the MEF2C isoform and the ASD. In this review, we summarized a concise overview of the general regulation, structure and functional roles of the MEF2C transcription factor. We further outlined the potential role of MEF2C as a risk factor for various neurodevelopmental disorders, such as ASD, MEF2C Haploinsufficiency Syndrome and Fragile X syndrome.

20.
ACS Appl Mater Interfaces ; 13(15): 18338-18347, 2021 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-33835791

RESUMEN

Surfactants are frequently employed in the fabrication of polymer/graphene-based nanocomposites via emulsion techniques. However, the impact of surfactants on the electrical and mechanical properties of such nanocomposite films remains to be explored. We have systematically studied the impact of two anionic surfactants [sodium dodecyl sulfate (SDS) and sodium dodecyl benzene sulfonate (SDBS)] on intrinsic properties of the nanocomposite films comprising reduced graphene oxide in a matrix of poly(styrene-stat-n-butyl acrylate). Using these ambient temperature film-forming systems, we fabricated films with different concentrations of the surfactants (1-7 wt %, relative to the organic phase). Significant differences in film properties were observed both as a function of amount and type of surfactant. Thermally reduced films exhibited concentration-dependent increases in surface roughness, electrical conductivity, and mechanical properties with increasing SDS content. When compared with SDBS, SDS films exhibited an order of magnitude higher electrical conductivity values at every concentration (highest value of ∼4.4 S m-1 for 7 wt % SDS) and superior mechanical properties at higher surfactant concentrations. The present results illustrate how the simple inclusion of a benzene ring in the SDS structure (as in SDBS) can cause a significant change in the electrical and mechanical properties of the nanocomposite. Overall, the present results demonstrate how nanocomposite properties can be judiciously manipulated by altering the concentration and/or type of surfactant.

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