ABSTRACT
Respiratory diseases (RD) are a group of common ailments with a rapidly increasing global prevalence, posing a significant threat to humanity, especially the elderly population, and imposing a substantial burden on society and the economy. RD represents an unmet medical need that requires the development of viable pharmacotherapies. While various promising strategies have been devised to advance potential treatments for RD, their implementation has been hindered by difficulties in drug delivery, particularly in critically ill patients. Nanotechnology offers innovative solutions for delivering medications to the inflamed organ sites, such as the lungs. Although this approach is enticing, delivering nanomedicine to the lungs presents complex challenges that require sophisticated techniques. In this context, we review the potential of novel nanomedicine-based immunomodulatory strategies that could offer therapeutic benefits in managing this pressing health condition.
Subject(s)
Nanoparticles , Respiratory Tract Diseases , Aged , Humans , Nanomedicine/methods , Drug Delivery Systems/methods , Immunomodulation , LungABSTRACT
The development of early non-invasive diagnosis methods and identification of novel biomarkers are necessary for managing Alzheimer's disease (AD) and facilitating effective prognosis and treatment. AD has multi-factorial nature and involves complex molecular mechanism, which causes neuronal degeneration. The primary challenges in early AD detection include patient heterogeneity and lack of precise diagnosis at the preclinical stage. Several cerebrospinal fluid (CSF) and blood biomarkers have been proposed to show excellent diagnosis ability by identifying tau pathology and cerebral amyloid beta (Aß) for AD. Intense research endeavors are being made to develop ultrasensitive detection techniques and find potent biomarkers for early AD diagnosis. To mitigate AD worldwide, understanding various CSF biomarkers, blood biomarkers, and techniques that can be used for early diagnosis is imperative. This review attempts to provide information regarding AD pathophysiology, genetic and non-genetic factors associated with AD, several potential blood and CSF biomarkers, like neurofilament light, neurogranin, Aß, and tau, along with biomarkers under development for AD detection. Besides, numerous techniques, such as neuroimaging, spectroscopic techniques, biosensors, and neuroproteomics, which are being explored to aid early AD detection, have been discussed. The insights thus gained would help in finding potential biomarkers and suitable techniques for the accurate diagnosis of early AD before cognitive dysfunction.
Subject(s)
Alzheimer Disease , Humans , Alzheimer Disease/diagnosis , Alzheimer Disease/pathology , Amyloid beta-Peptides , tau Proteins , Early Diagnosis , BiomarkersABSTRACT
This study reports the simultaneous delivery of EGFP siRNA and the chemotherapeutic drug, doxorubicin by means of the composition that results from the electrostatic interaction between positively charged siRNA-complexes of gold nanoparticles (AuNPs) capped with PEI, 25kDa (P25-AuNPs) and negatively charged carboxymethyl cellulose formulated PLGA nanoparticles loaded with doxorubicin. The nanoparticles and their facile interaction were studied by means of dynamic light scattering (DLS), zeta potential, transmission electron microscopic (TEM) measurements. The flow cytometric and confocal microscopic analysis evidenced the simultaneous internalization of both labelled siRNA and doxorubin into around 55% of the HeLa cancer cell population. Fluorescence microscopic studies enabled the visual analysis of EGFP expressing HeLa cells which suggested that the composition mediated codelivery resulted in a substantial downregulation of EGFP expression and intracellular accumulation of doxorubicin. Interestingly, codelivery treatment resulted in an increased cellular delivery of doxorubicin when compared to PLGA-DOX alone treatment. On the other hand, the activity of siRNA complexes of PEI-AuNPs was completely retained even when they were part of composition. The results suggest that this formulation can serve as promising tool for delivery applications in combinatorial anticancer therapy.
Subject(s)
Antineoplastic Agents/pharmacology , Doxorubicin/pharmacology , Gold/chemistry , Lactic Acid/chemistry , Metal Nanoparticles/chemistry , Polyethyleneimine/chemistry , Polyglycolic Acid/chemistry , RNA, Small Interfering/pharmacology , Antineoplastic Agents/chemistry , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Doxorubicin/chemistry , Drug Delivery Systems , Drug Screening Assays, Antitumor , Green Fluorescent Proteins/chemistry , HeLa Cells , Humans , Molecular Structure , Particle Size , Polylactic Acid-Polyglycolic Acid Copolymer , RNA, Small Interfering/chemistry , Structure-Activity Relationship , Surface PropertiesABSTRACT
A simple, mild, green, catalytic and general procedure for the direct synthesis of highly functionalized 1-methoxycarbonyl-2-aryl/alkyl-3-nitro-9H-carbazoles has been achieved in water medium via a one-pot domino Michael-Henry/aromatization reaction of methyl 2-(3-formyl-1H-indol-2-yl)acetates with aryl/alky-substituted ß-nitroolefins under air using DABCO (30 mol%) as an organocatalyst. In addition, the bench scale synthesis can be performed without using toxic organic solvents and a biologically important new fused carbazole has been prepared.
Subject(s)
Carbazoles/chemical synthesis , Water/chemistry , Carbazoles/chemistry , Catalysis , Green Chemistry Technology , Piperazines/chemistryABSTRACT
A simple, mild and robust method for the stereoselective synthesis of (E)-methyl α-(3-formyl-1H-indol-2-yl)-ß-aryl/alkyl-substituted acrylates via a condensation reaction of methyl 2-(3-formyl-1H-indol-2-yl)acetate with several alkyl or aryl aldehydes using L-proline (25 mol%) as a catalyst is presented for the first time. In addition, completely metal free based high yielding methods for the syntheses of highly substituted biologically important carbazoles, γ-carbolines and the marine alkaloid prenostodione have been developed through our methodology.
Subject(s)
Acrylates/chemical synthesis , Carbazoles/chemical synthesis , Carbolines/chemical synthesis , Indoles/chemical synthesis , Proline/chemistry , Acrylates/chemistry , Carbazoles/chemistry , Carbolines/chemistry , Catalysis , Indoles/chemistry , Molecular Structure , StereoisomerismABSTRACT
BACKGROUND: Coronaviruses such as Severe Acute Respiratory Syndrome coronavirus (SARS), Middle Eastern Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) are associated with critical illnesses, including severe respiratory disorders. SARS-CoV-2 is the causative agent of the deadly COVID-19 illness, which has spread globally as a pandemic. SARS-CoV-2 may enter the human body through olfactory lobes and interact with the angiotensin-converting enzyme2 (ACE2) receptor, further facilitating cell binding and entry into the cells. Reports have shown that the virus can pass through the blood-brain barrier (BBB) and enter the central nervous system (CNS), resulting in various disorders. Cell entry by SARS-CoV-2 largely relies on TMPRSS2 and cathepsin L, which activate S protein. TMPRSS2 is found on the cell surface of respiratory, gastrointestinal and urogenital epithelium, while cathepsin-L is a part of endosomes. AIM: The current review aims to provide information on how SARS-CoV-2 infection affects brain function.. Furthermore, CNS disorders associated with SARS-CoV-2 infection, including ischemic stroke, cerebral venous thrombosis, Guillain-Barré syndrome, multiple sclerosis, meningitis, and encephalitis, are discussed. The many probable mechanisms and paths involved in developing cerebrovascular problems in COVID patients are thoroughly detailed. MAIN BODY: There have been reports that the SARS-CoV-2 virus can cross the blood-brain barrier (BBB) and enter the central nervous system (CNS), where it could cause a various illnesses. Patients suffering from COVID-19 experience a range of neurological complications, including sleep disorders, viral encephalitis, headaches, dysgeusia, and cognitive impairment. The presence of SARS-CoV-2 in the cerebrospinal fluid (CSF) of COVID-19 patients has been reported. Health experts also reported its presence in cortical neurons and human brain organoids. The possible mechanism of virus infiltration into the brain can be neurotropic, direct infiltration and cytokine storm-based pathways. The olfactory lobes could also be the primary pathway for the entrance of SARS-CoV-2 into the brain. CONCLUSIONS: SARS-CoV-2 can lead to neurological complications, such as cerebrovascular manifestations, motor movement complications, and cognitive decline. COVID-19 infection can result in cerebrovascular symptoms and diseases, such as strokes and thrombosis. The virus can affect the neural system, disrupt cognitive function and cause neurological disorders. To combat the epidemic, it is crucial to repurpose drugs currently in use quickly and develop novel therapeutics.
Subject(s)
COVID-19 , SARS-CoV-2 , Humans , COVID-19/complications , Central Nervous System , Brain , Blood-Brain BarrierABSTRACT
The integrity of the blood-brain barrier (BBB) is essential for normal central nervous system (CNS) functioning. Considering the significance of BBB in maintaining homeostasis and the neural environment, we aim to provide an overview of significant aspects of BBB. Worldwide, the treatment of neurological diseases caused by BBB disruption has been a major challenge. BBB also restricts entry of neuro-therapeutic drugs and hinders treatment modalities. Hence, currently nanotechnology-based approaches are being explored on large scale as alternatives to conventional methodologies. It is necessary to investigate the in-depth characteristic features of BBB to facilitate the discovery of novel drugs that can successfully cross the barrier and target the disease effectively. It is imperative to discover novel strategies to treat life-threatening CNS diseases in humans. Therefore, insights regarding building blocks of BBB, activation of immune response on breach of this barrier, and various autoimmune neurological disorders caused due to BBB dysfunction are discussed. Further, special emphasis is given on delineating BBB disruption leading to CNS disorders. Moreover, various mechanisms of transport pathways across BBB, several novel strategies, and alternative routes by which drugs can be properly delivered into CNS are also discussed.
Subject(s)
Blood-Brain Barrier , Central Nervous System Diseases , Biological Transport , Blood-Brain Barrier/metabolism , Central Nervous System Diseases/drug therapy , Drug Delivery Systems/methods , Humans , NanotechnologyABSTRACT
Antimicrobial peptides (AMPs) attracted attention as potential source of novel antimicrobials. Multi-drug resistant (MDR) infections have emerged as a global threat to public health in recent years. Furthermore, due to rapid emergence of new diseases, there is pressing need for development of efficient antimicrobials. AMPs are essential part of the innate immunity in most living organisms, acting as the primary line of defense against foreign invasions. AMPs kill a wide range of microorganisms by primarily targeting cell membranes or intracellular components through a variety of ways. AMPs can be broadly categorized based on their physico-chemical properties, structure, function, target and source of origin. The synthetic analogues produced either with suitable chemical modifications or with the use of suitable delivery systems are projected to eliminate the constraints of toxicity and poor stability commonly linked with natural AMPs. The concept of peptidomimetics is gaining ground around the world nowadays. Among the delivery systems, nanoparticles are emerging as potential delivery tools for AMPs, amplifying their utility against a variety of pathogens. In the present review, the broad classification of various AMPs, their mechanism of action (MOA), challenges associated with AMPs, current applications, and novel strategies to overcome the limitations have been discussed.