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1.
J Pharm Anal ; 11(5): 529-540, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34178413

RESUMO

The deadly global outbreak of coronavirus disease-2019 (COVID-19) has forged an unrivaled threat to human civilization. Contemplating its profuse impact, initial risk management and therapies are needed, as well as rapid detection strategies alongside treatments with existing drugs or traditional treatments to provide better clinical support for critical patients. Conventional detection techniques have been considered but do not sufficiently meet the current challenges of effective COVID-19 diagnosis. Therefore, several modern techniques including point-of-care diagnosis with a biosensor, clustered regularly interspaced short palindromic repeats (CRISPR)-associated proteins that function as nuclease (Cas) technology, next-generation sequencing, serological, digital, and imaging approaches have delivered improved and noteworthy success compared to that using traditional strategies. Conventional drug treatment, plasma therapy, and vaccine development are also ongoing. However, alternative medicines including Ayurveda, herbal drugs, homeopathy, and Unani have also been enlisted as prominent treatment strategies for developing herd immunity and physical defenses against COVID-19. All considered, this review can help develop rapid and simplified diagnostic strategies, as well as advanced evidence-based modern therapeutic approaches that will aid in combating the global pandemic.

2.
Mol Biol Rep ; 47(5): 3745-3763, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32361897

RESUMO

Cancer cells need extensive energy supply for their uncontrolled cell division and metastasis which is exclusively dependent on neighboring cells, especially adipocytes. Herein, we have introduced a novel herbometallic nano-drug, Heerak Bhasma nanoparticle (HBNP) from natural resources showing high potential in the reduction of energy supply thereby promoting cell death in breast cancer cells. Inductively coupled plasma optical emission spectra (ICP-OES), atomic absorption spectra (AAS), Raman spectra, X-ray diffraction analyses confirmed the physicochemical properties of HBNP. The differential light scattering (DLS) and field emission scanning electron microscope (FESEM) analyzed the cell-permeable size of HBNP, whereas, cell viability assay confirmed the non-toxic effect. Seahorse energy efflux assay, apoptotic cell quantification, ROS, mitochondrial membrane potential, in vivo oxidative stress etc. were measured using standard protocol. The notable changes in cancer energy metabolism investigated by cellular Mito and Glyco-stress analyses confirmed the HBNP induced intracellular energy depletion. Also, a significant reduction in mitochondrial membrane potential and subsequently, extensive reactive oxygen species (ROS) generations were observed in presence of HBNP followed by the induction of cell apoptosis. The cell invasion and wound healing assay followed by reduced expression both protein (MMP 2, MMP 9) and cytokine (IL6, IL10) had signified the effectiveness of HBNP against cancer metastasis. In addition, HBNP also showed an excellent antitumor activity in vivo followed by developing healing characteristics due to oxidative stress. All these findings strongly suggest that HBNP has the potential to be the new cancer therapeutic. A schematic phenomenon represents the overall HBNP mediated anticancer activity via limitation of both fatty acid uptake and energy metabolism.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Medicina Ayurvédica/métodos , Nanopartículas Metálicas/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Metabolismo Energético/fisiologia , Feminino , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo
3.
Nanomedicine (Lond) ; 14(9): 1173-1189, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31050596

RESUMO

Aim: Preparation of a herbometallic nano-drug, Rasa Manikya nanoparticle (RMNP) and investigation of its antimicrobial, and anticancer activity. Materials & methods: Physicochemical characterizations of RMNP were performed using different analytical methods. The antimicrobial and anticancer potential of RMNPs were assessed by an in vitro cellular assay. Bacterial cell wall lysis was observed by field emission scanning electron microscopy and mitochondrial metabolism alteration factor was measured via standard method. Results: Physicochemical analysis confirmed that RMNP was rich in mineral constituents. Synergistic effect of RMNPs enhanced lysis of bacterial peptidoglycan layers and impaired cellular redox balance, GSH/NADPH level followed by induction of cell apoptosis. Conclusion: The present study confirms that RMNP can be used as a dual therapeutic option for combating drug-resistant microbial strains and breast cancer.


Assuntos
Antibacterianos/química , Antineoplásicos/química , Arsenicais/química , Nanopartículas Metálicas/química , Estresse Oxidativo , Preparações de Plantas/química , Sulfetos/química , Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Arsenicais/farmacologia , Linhagem Celular , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Enterobacter/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Humanos , Medicina Ayurvédica , Testes de Sensibilidade Microbiana , Oxirredução , Preparações de Plantas/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Sulfetos/farmacologia
4.
Mol Neurobiol ; 56(9): 6551-6565, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30868446

RESUMO

The amyloid cascade hypothesis dealing with the senile plaques is until date thought to be one of the causative pathways leading to the pathophysiology of Alzheimer's disease (AD). Though many aggregation inhibitors of misfolded amyloid beta (Aß42) peptide have failed in clinical trials, there are some positive aspects of the designed therapeutic peptides for diseases involving proteinaceous aggregation. Here, we evaluated a smart design of side chain tripeptide (Leu-Val-Phe)-based polymeric inhibitor addressing the fundamental hydrophobic amino acid stretch "Lys-Leu-Val-Phe-Phe-Ala" (KLVFFA) of the Aß42 peptide. The in vitro analyses performed through the thioflavin T (ThT) fluorescence assay, infrared spectroscopy, isothermal calorimetry, cytotoxicity experiments, and so on evinced a promising path towards the development of new age AD therapeutics targeting the inhibition of misfolded Aß42 peptide fibrillization. The in silico simulations done contoured the mechanism of drug action of the present block copolymer as the competitive inhibition of aggregate-prone hydrophobic stretch of Aß42. Graphical abstract The production of misfolded Aß42 peptide from amyloid precursor protein initiates amyloidosis pathway which ends with the deposition of fibrils via the oligomerization and aggregation of Aß42 monomers. The side chain tripeptide-based PEGylated polymer targets these Aß42 monomers and oligomers inhibiting their aggregation. This block copolymer also binds and helps degrading the preformed fibrils of Aß42.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Polietilenoglicóis/química , Peptídeos beta-Amiloides/química , Peptídeos beta-Amiloides/metabolismo , Peptídeos beta-Amiloides/ultraestrutura , Morte Celular , Linhagem Celular Tumoral , Sobrevivência Celular , Humanos , Ligantes , Simulação de Dinâmica Molecular , Polietilenoglicóis/síntese química , Eletricidade Estática
5.
Int J Neurosci ; 128(5): 449-463, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29076790

RESUMO

Misfolded ß-sheet structures of proteins leading to neurodegenerative diseases like Alzheimer's disease (AD) and Parkinson's disease (PD) are in the spotlight since long. However, not much was known about the functional amyloids till the last decade. Researchers have become increasingly more concerned with the degree of involvement of these functional amyloids in human physiology. Interestingly, it has been found that the human body is exposed to a tremendous systemic amyloid burden, especially, during aging. Although many findings regarding these functional amyloids come up every day, some questions still remain unanswered like do these functional amyloids directly involve in the fibrillization of amyloid beta (Aß) 42 peptide or enhance the Aß42 aggregation rate; whether functional bacterial amyloids (FuBA) co-localize with the senile plaques of AD or not. A detailed review of the latest status regarding the interrelationship between functional amyloids, pathogenic amyloids and misfolded prions and therapeutic assessment of functional amyloids for the treatment of neurodegenerative diseases can help identify an alternative medication for neurodegeneration. A unique mathematical model is proposed here for alteration of Aß42 aggregation kinetics in AD to carve out the future direction of therapeutic consideration.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Amiloide/metabolismo , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/terapia , Amiloide/química , Evolução Biológica , Simulação por Computador , Humanos , Modelos Biológicos , Doenças Neurodegenerativas/etiologia , Proteínas Priônicas/metabolismo , Deficiências na Proteostase/complicações
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