As a key inflammatory factor, the nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome plays a crucial role in neuroinflammation and the progression of neurodegenerative diseases. Dysregulation of NLRP3 signaling can trigger various inflammatory responses in the brain, contributing to the development of neurodegenerative diseases such as ischemic stroke, vascular dementia (VaD), Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). Therefore, the NLRP3 signaling pathway is a promising therapeutic target for the treatment of neurodegenerative diseases, including VaD.
View Article and Find Full Text PDFThis review comprehensively covers the translation from batch to continuous flow synthesis of metal nanowires (, silver, copper, gold, and platinum nanowires) and their diverse applications across various sectors. Metal nanowires have attracted significant attention owing to their versatility and feasibility for large-scale synthesis. The efficacy of flow chemistry in nanomaterial synthesis has been extensively demonstrated over the past few decades.
View Article and Find Full Text PDFIntroduction: A survey-based approach to managing antibiotic-resistant infections in the intensive care unit (ICU) setting, with a focus on carbapenem-resistant Enterobacteriaceae (CRE) cases, was conducted. Among CRE, New Delhi metallo-β-lactamase 1 (NDM-1) is a carbapenemase that is resistant to β-lactam antibiotics and has a broader spectrum of antimicrobial resistance than other carbapenemase types. The article explains that healthcare-associated infections (HAIs) are a significant problem, particularly in low- and middle-income countries, and that carbapenem in combination with other antibiotics are the most potent class of antimicrobial agents effective in treating life-threatening bacterial infections, including those caused by resistant strains.
View Article and Find Full Text PDFSpectrochim Acta A Mol Biomol Spectrosc
January 2024
Targeted drug delivery (TDD) is a method of delivering optimum concentrations of pharmaceutical substances in the tissue to achieve the desired therapeutic effect. Hence, TDD systems are considered as an emerging strategy to deliver the drug at the specific site of the tissues/cells. The nanoparticle-protein corona as a drug delivery vehicle has demonstrated immense benefits including potential theragnostic, improved pharmacodynamics and targeted drug delivery.
View Article and Find Full Text PDFThe dynamics of drop formation have been investigated in the presence of interfacial mass transfer through controlled flow visualization experiments. The mixtures of -hexane (solvent) and acetone (solute) were used as a dispersed phase, having different initial compositions varying over a broad range. Drops were formed at the submerged position in the continuous phase (water) at the same operating flow conditions.
View Article and Find Full Text PDFA simple and efficient solvent-free protocol for continuous flow synthesis of amides at room temperature is developed using easily available starting materials. -(3-Dimethylaminopropyl)-'-ethylcarbodiimide hydrochloride (EDC.HCl) was used as the reagent for the formation of an amide bond without using any metal catalyst or additives.
View Article and Find Full Text PDFIn this study, a heterogeneous nucleation and growth model has been developed to explore the formation mechanism of silver-deposited silica core-shell particles based on the reaction kinetics. To validate the core-shell model, the time-dependent experimental data were quantitatively examined and reduction, nucleation, and growth rates were estimated by optimizing the concentration profiles of reactants and deposited silver particles. Using this model, we also attempted to predict the change in the surface area and diameter of core-shell particles.
View Article and Find Full Text PDFIdentifying failure modes is an important task to improve the design and reliability of a product and can also serve as a key input in sensor selection for predictive maintenance. Failure mode acquisition typically relies on experts or simulations which require significant computing resources. With the recent advances in Natural Language Processing (NLP), efforts have been made to automate this process.
View Article and Find Full Text PDFMitral valve prolapse is a commonly described entity with a highly variable and benign course. However, it is associated with ventricular arrhythmias and sudden cardiac death in a small subset of patients. Recent studies have yielded insight into myocardial mechanics and the causation of ventricular arrhythmias in these groups of patients.
View Article and Find Full Text PDFRetin Cases Brief Rep
September 2023
Background/purpose: The purpose of this study was to report a case series of full-thickness macular holes without vitreomacular traction that resolved without surgery.
Methods: This study is a retrospective case series of 11 patients who demonstrated closure of full-thickness macular holes without surgical intervention.
Results: All full-thickness macular holes closed, with all patients having improvement in visual acuity.
The nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome plays an important role in microglia-mediated inflammation. Dysregulation of NLRP3 signaling results in microglial activation and triggers inflammatory responses contributing to the development of neurological disorders including ischemic stroke, schizophrenia, Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). Inhibition of the NLRP3-linked inflammatory pathways reduces microglia-induced inflammation and is considered as a promising therapeutic approach for neuro-inflammatory diseases.
View Article and Find Full Text PDFHerein we report for the first time, an advanced continuous flow synthesis of the blockbuster Leishmaniasis drug miltefosine from simple starting materials by a sequence involving four steps of chemical transformation including a continuous mechanochemical step. First three reaction steps were performed in simple tubular reactors in a telescopic mode, while in the last step the product precipitated from the 3 step was used for a continuous mechanochemical synthesis of miltefosine. When compared to a typical batch protocol that takes 15 h, miltefosine was obtained in 58 % overall yield in flow synthesis mode at the laboratory scale in a total residence time 34 min at synthesis rate of 10 g/hr, which is sufficient to treat 4800 patients per day.
View Article and Find Full Text PDFIn a world of rapidly changing technologies, reliance on complex engineered systems has become substantial. Interactions associated with such systems as well as associated manufacturing processes also continue to evolve and grow in complexity. Consider how the complexity of manufacturing processes makes engineered systems vulnerable to cascading and escalating failures; truly a highly complex and evolving system of systems.
View Article and Find Full Text PDFHIV-1 infection impairs cellular cholesterol efflux by downmodulating the cholesterol transporter ABCA1, leading to metabolic co-morbidities like cardio-vascular disease. The main mechanism of this effect is impairment by the HIV-1 protein Nef of the ABCA1 interaction with the endoplasmic reticulum chaperone calnexin, which leads to a block in ABCA1 maturation followed by its degradation. However, ABCA1 is also downmodulated by Nef delivered with the extracellular vesicles, suggesting involvement of a direct Nef:ABCA1 interaction at the plasma membrane.
View Article and Find Full Text PDFDespite the crucial role of Polymyxin-B in treating life-threatening gram-negative infections, its clinical utility is limited due to the risk of acute kidney injury. In response, a novel formulation of polymyxin-B is being developed to mitigate drug-induced kidney injury. In this study, we have assessed the toxicity of four variants of that novel formulation (VRP034_F21-F24) in comparison with standard polymyxin-B using kidney injury biomarkers in rats.
View Article and Find Full Text PDFRecent Pat Food Nutr Agric
January 2022
Background: Aloe vera is a plant traditionally used for medicinal purposes. It is also used as a cosmetic. Aloe vera gel/extract/juice is used in hair care, moisturizing, cleansing, and thickening agent in formulations.
View Article and Find Full Text PDFHybridization is an important strategy to design molecules that can be effectively used to treat fatal diseases known to mankind. Molecular hybrids and their pharmacological investigations aided in discovering several potent isatin (Indole 2, 3 dione) derivatives with anti-HIV, antimalarial, antitubercular, antibacterial, and anticancer activities. Indole-2,3-dione and their derivatives have diverse pharmacological properties and have a prominent role in the discovery of new drugs.
View Article and Find Full Text PDFCombination antiretroviral therapy (cART) suppresses human immunodeficiency virus-1 (HIV-1) replication but is unable to permanently eradicate HIV-1. Importantly, cART does not target HIV-1 transcription, which is reactivated in latently infected reservoirs, leading to HIV-1 pathogenesis including non-infectious lung, cardiovascular, kidney, and neurodegenerative diseases. To address the limitations of cART and to prevent HIV-1-related pathogenesis, we developed small molecules to target the noncatalytic RVxF-accommodating site of protein phosphatase-1 (PP1) to prevent HIV-1 transcription activation.
View Article and Find Full Text PDFSilver nanowires (AgNWs) are known to be used for printing on rigid as well as flexible surfaces. Here we have developed a systematic approach for using AgNWs synthesized by the polyol method for printing on flexible surfaces using a simple inkjet printing method. Optimized ink formulation used in this work comprises a mixture of Ag NWs suspended in ethylene glycol directly taken after synthesis and isopropyl alcohol.
View Article and Find Full Text PDFInflammasomes are multiprotein assemblies that produce robust inflammatory responses upon stimulation with pathogen- and/or danger-associated molecular patterns. Uncontrolled inflammasome activation has been linked to the pathophysiology of a wide array of disorders including life-threatening pathogenic infections, e.g.
View Article and Find Full Text PDFObjective: Surgeon tremor was measured during vitreoretinal microscopic surgeries under different hand support conditions.
Background: While the ophthalmic surgeon's forearm is supported using a standard symmetric wrist rest when operating on the patient's same side as the dominant hand (SSD), the surgeon's hand is placed directly on the patient's forehead when operating on the contralateral side of the dominant hand (CSD). It was hypothesized that more tremor is associated with CSD surgeries than SSD surgeries and that, using an experimental asymmetric wrist rest where the contralateral wrist bar gradually rises and curves toward the patient's operative eye, there is no difference in tremor associated with CSD and SSD surgeries.
Analytical method for the determination of related substances (RS) in Daclatasvir tablets was optimised using quality by design (QbD) approach. Seven degradants (each more than 1.0%) generated during oxidation study, adversely affected the selectivity of the method.
View Article and Find Full Text PDFLevonadifloxacin is a novel benzoquinolizine subclass of fluoroquinolone, active against quinolone-resistant A phase 3 trial for levonadifloxacin and its oral prodrug was recently completed. The present study identified area under the concentration-time curve for the free, unbound fraction of a drug divided by the MIC (AUC/MIC) as an efficacy determinant for levonadifloxacin in a neutropenic murine lung infection model. Mean plasma AUC/MIC requirement for static and 1 log kill effects against 9 were 8.
View Article and Find Full Text PDFPurpose: The WHO framework for early cancer diagnosis highlights the need to improve health care capacity among primary care providers. In Rwanda, general practitioners (GPs) at district hospitals (DHs) play key roles in diagnosing, initiating management, and referring suspected patients with cancer. We sought to ascertain educational and resource needs of GPs to provide a blueprint that can inform future early cancer diagnosis capacity-building efforts.
View Article and Find Full Text PDFThe dengue virus is considered to be a globally important human pathogen prevalent in tropical and subtropical regions of the world. According to a recent estimate, the disease burden due to DENV infections is ∼390 million infections per year globally in ∼100 countries including the southern US, Puerto Rico and Hawaii, resulting in nearly ∼25,000 deaths mostly among children. Despite the significant morbidity and mortality that results from DENV infections, there is currently no effective chemotherapeutic treatment for DENV infections.
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