Biomedical nanotechnology is an evolving field having enormous potential to positively impact the health care system. Important biomedical applications of nanotechnology that may have potential ...clinical applications include targeted drug delivery, detection/diagnosis and imaging. Basic understanding of how nanomaterials, the building blocks of nanotechnology, interact with the cells and their biological consequences are beginning to evolve. Noble metal nanoparticles such as gold, silver and platinum are particularly interesting due to their size and shape dependent unique optoelectronic properties. These noble metal nanoparticles, particularly of gold, have elicited a lot of interest for important biomedical applications because of their ease of synthesis, characterization and surface functionalization. Furthermore, recent investigations are demonstrating another promising application of these nanomaterials as self-therapeutics. To realize the potential promise of these unique inorganic nanomaterials for future clinical translation, it is of utmost importance to understand a few critical parameters; (i) how these nanomaterials interact with the cells at the molecular level; (ii) how their biodistribution and pharmacokinetics influenced by their surface and routes of administration; (iii) mechanism of their detoxification and clearance and (iv) their therapeutic efficacy in appropriate disease model. Thus in this critical review, we will discuss the various clinical applications of gold, silver and platinum nanoparticles with relevance to above parameters. We will also mention various routes of synthesis of these noble metal nanoparticles. However, before we discuss present research, we will also look into the past. We need to understand the discoveries made before us in order to further our knowledge and technological development (318 references).
Abstract
In a household study, loss of taste and/or smell was the fourth most reported symptom (26/42 62%) among coronavirus disease 2019 (COVID-19) case patients and had the highest positive ...predictive value (83% 95% confidence interval CI, 55%–95%) among household contacts. Olfactory and taste dysfunctions should be considered for COVID-19 case identification and testing prioritization.
Neurodegenerative diseases (NDs) are characterised by progressive dysfunction of synapses, neurons, glial cells and their networks. Neurodegenerative diseases can be classified according to primary ...clinical features (e.g., dementia, parkinsonism, or motor neuron disease), anatomic distribution of neurodegeneration (e.g., frontotemporal degenerations, extrapyramidal disorders, or spinocerebellar degenerations), or principal molecular abnormalities. The most common neurodegenerative disorders are amyloidosis, tauopathies, a-synucleinopathy, and TAR DNA-binding protein 43 (TDP-43) proteopathy. The protein abnormalities in these disorders have abnormal conformational properties along with altered cellular mechanisms, and they exhibit motor deficit, mitochondrial malfunction, dysfunctions in autophagic–lysosomal pathways, synaptic toxicity, and more emerging mechanisms such as the roles of stress granule pathways and liquid-phase transitions. Finally, for each ND, microglial cells have been reported to be implicated in neurodegeneration, in particular, because the microglial responses can shift from neuroprotective to a deleterious role. Growing experimental evidence suggests that abnormal protein conformers act as seed material for oligomerization, spreading from cell to cell through anatomically connected neuronal pathways, which may in part explain the specific anatomical patterns observed in brain autopsy sample. In this review, we mention the human pathology of select neurodegenerative disorders, focusing on how neurodegenerative disorders (i.e., Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and multiple sclerosis) represent a great healthcare problem worldwide and are becoming prevalent because of the increasing aged population. Despite many studies have focused on their etiopathology, the exact cause of these diseases is still largely unknown and until now with the only available option of symptomatic treatments. In this review, we aim to report the systematic and clinically correlated potential biomarker candidates. Although future studies are necessary for their use in early detection and progression in humans affected by NDs, the promising results obtained by several groups leads us to this idea that biomarkers could be used to design a potential therapeutic approach and preclinical clinical trials for the treatments of NDs.
The latest estimates from world health organization suggest that more than 450 million people are suffering from depression and other psychiatric conditions. Of these, 50–60% have been reported to ...have progression of gut diseases. In the last two decades, researchers introduced incipient physiological roles for serotonin (5-HT) receptors (5-HTRs), suggesting their importance as a potential pharmacological target in various psychiatric and gut diseases. A growing body of evidence suggests that 5-HT systems affect the brain-gut axis in depressive patients, which leads to gut comorbidity. Recently, preclinical trials of 5-HT4R agonists and antagonists were promising as antipsychotic and prokinetic agents. In the current review, we address the possible pharmacological role and contribution of 5-HT4R in the pathophysiology of chronic depression and associated gut abnormalities. Physiologically, during depression episodes, centers of the sympathetic and parasympathetic nervous system couple together with neuroendocrine systems to alter the function of hypothalamic-pituitary-adrenal (HPA) axis and enteric nervous system (ENS), which in turn leads to onset of gastrointestinal tract (GIT) disorders. Consecutively, the ENS governs a broad spectrum of physiological activities of gut, such as visceral pain and motility. During the stages of emotional stress, hyperactivity of the HPA axis alters the ENS response to physiological and noxious stimuli. Consecutively, stress-induced flare, swelling, hyperalgesia and altered reflexes in gut eventually lead to GIT disorders. In summary, the current review provides prospective information about the role and mechanism of 5-HT4R-based therapeutics for the treatment of depressive disorder and possible consequences for the gut via brain-gut axis interactions.
This article is part of the special issue entitled ‘Serotonin Research: Crossing Scales and Boundaries’.
•Expression profile of 5-HT4R in various brain and gut regions.•Pharmacological and genomic evidences of 5-HT4R association with depression.•Role of 5-HT4R in the brain-gut axis activation and gut function.•Expression and function of 5-HT4R in ENS.•Clinical significance of potential 5-HT4R agonists and antagonists.
We report an inducible epitope imprinting strategy that as a template, a flexible peptide chain can have a disordered-to-ordered conformational change by suitable inducement through a molecular ...imprinting procedure, and the formed nanoparticles can, in turn, remold the original peptide into the expected conformation and specifically bind to the corresponding protein.
Treatment with monoclonal antibody (mAbs) is a viable therapeutic option in cancer. Recently, these mAbs such as cetuximab, herceptin, etc., have been used as targeting agents to selectively deliver ...chemotherapeutics to cancerous cells. However, mechanisms of nanoparticles-mAbs interactions with the target cells and its effect on intracellular trafficking and mechanism are currently unknown. In this paper, we demonstrate that the distinct patterning and dynamics of anti-EGFR (epidermal growth factor receptor) antibody cetuximab (C225)- induced EGFR internalization in pancreatic cancer cells with variable receptor expression is altered upon nanoconjugation. Nanoconjugation uniformly enhanced C225-induced EGFR endocytosis in PANC-1, AsPC-1, and MiaPaca-2 cells, influenced its compartmentalization and regulated the involvement of dynamin-2 in the endocytic processes. Receptor endocytosis and its intracellular trafficking were monitored by confocal microscopy and transmission electron microscopy. The role of dynamin-2 in EGFR endocytosis was determined after overexpressing either wild-type dynamin-2 or mutant dynamin-2 in pancreatic cancer cells followed by tracking the receptor-antibody complex internalization by confocal microscopy. Significantly, these findings demonstrate that the nanoconjugation cannot be construed as an innocuous reaction involved in attaching the targeting agent to the nanoparticle, instead it may distinctly alter the cellular processes at the molecular level, at least antibody induced receptor endocytosis. This information is critical for successful design of a nanoparticle-based targeted drug delivery system for future clinical translation.
Epithelial ovarian cancer is the leading cause of gynecologic cancer deaths. Most patients respond initially to platinum-based chemotherapy after surgical debulking, however relapse is very common ...and ultimately platinum resistance emerges. Understanding the mechanism of tumor growth, metastasis and drug resistant relapse will profoundly impact the therapeutic management of ovarian cancer.
Using patient tissue microarray (TMA), in vitro and in vivo studies we report a role of of cystathionine-beta-synthase (CBS), a sulfur metabolism enzyme in ovarian carcinoma. We report here that the expression of cystathionine-beta-synthase (CBS), a sulfur metabolism enzyme, is common in primary serous ovarian carcinoma. The in vitro effects of CBS silencing can be reversed by exogenous supplementation with the GSH and H2S producing chemical Na2S. Silencing CBS in a cisplatin resistant orthotopic model in vivo by nanoliposomal delivery of CBS siRNA inhibits tumor growth, reduces nodule formation and sensitizes ovarian cancer cells to cisplatin. The effects were further corroborated by immunohistochemistry that demonstrates a reduction of H&E, Ki-67 and CD31 positive cells in si-RNA treated as compared to scrambled-RNA treated animals. Furthermore, CBS also regulates bioenergetics of ovarian cancer cells by regulating mitochondrial ROS production, oxygen consumption and ATP generation. This study reports an important role of CBS in promoting ovarian tumor growth and maintaining drug resistant phenotype by controlling cellular redox behavior and regulating mitochondrial bioenergetics.
The present investigation highlights CBS as a potential therapeutic target in relapsed and platinum resistant ovarian cancer.
Reinforcement of natural rubber was achieved using carboxylated multiwalled carbon nanotubes (c-MWCNT) dispersed with sodium dodecyl sulfate. The structure of the reinforced latex films was ...investigated by TEM and AFM. The tensile and dynamic-mechanical tests demonstrated a strong enhancement in the Young’s modulus (∼10-fold), tensile strength (∼2-fold) and storage modulus (∼60-fold) at low-strain in the rubbery state with up to 8.3
wt% of MWCNTs, with a small reduction in elongation at break. Dielectric measurement at room temperature revealed a low percolation threshold (<1
wt%) associated with the formation of an interconnected nanotube network. Latex film formation plays a critical role in the network formation due to the segregation effect at the surface of latex beads. We observed large Payne and Mullins effects due to the mechanical behavior of the nanotube network. The disruption of the network during stretching induces both an increase of electrical resistivity and mechanical stress-softening.
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