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1.
Future Sci OA ; 10(1): FSO922, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38841181

RESUMO

Aim: Photobiomodulation involves the use of low-level light therapy or near-infrared light therapy found to be useful in the treatment of a wide range of neurological diseases. Objective: The aim is to review the mechanism and clinical applications of photobiomodulation therapy (PBMT) in managing Alzheimer's disease. Methods: To ensure that the consensus statement accurately reflects both the experts' viewpoint and the most recent developments in the field, the expert opinions were recorded and thoroughly reviewed. Results: PBMT elicits reduction of beta-amyloid plaque, restoration of mitochondrial function, anti-inflammatory and antioxidant properties with a stimulation in ATP synthesis. Conclusion: The PBMT could be helpful in patients non-responsive to traditional pharmacological therapy providing significant aid in the management of Alzheimer's disease when introduced into the medical field.


Alzheimer's disease (AD) is an incurable progressive neurodegenerative disease clinically manifested with a decline in cognitive function. To ensure that the consensus statement accurately reflects both the experts' viewpoint and the most recent developments in the field, the expert opinions were recorded and thoroughly reviewed. PBMT elicits various mechanisms such as reduction of beta-amyloid plaque, Restoration of mitochondrial function and maintenance the homeostasis, and anti-inflammatory and antioxidant properties with a stimulation in ATP synthesis. The PBMT could be helpful in patients who are non-responsive to conventional pharmacological therapy. This therapy might provide significant aid in the management of AD when introduced into the medical field. However, it requires various intensive research to be conducted for further conclusion.

3.
Biomedicines ; 12(4)2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38672144

RESUMO

A series of novel 1,5-diaryl pyrazole derivatives targeting the COX enzyme were designed by combined ligand and structure-based approach. The designed molecules were then further subjected to ADMET and molecular docking studies. Out of 34 designed compounds, the top-10 molecules from the computation studies were synthesized, characterized, and evaluated for COX-2 inhibition and anti-cancer activity. Initially, the target compounds were screened for the protein denaturation assay. The results of the top-five molecules T2, T3, T5, T6, and T9 were further subjected to in vitro COX-2 enzymatic assay and anti-cancer activity. As far as COX-2 inhibitory activity is considered, two compounds, T3 and T5, exhibited the half maximum inhibitory concentration (IC50) at 0.781 µM and 0.781 µM respectively. Further, the two compounds T3 and T5, when evaluated for COX-1 inhibition, exhibited excellent inhibitory activity with T3 IC50 of 4.655µM and T5 with IC50 of 5.596 µM. The compound T5 showed more significant human COX-2 inhibition, with a selectivity index of 7.16, when compared with T3, which had a selectivity index of 5.96. Further, in vitro anti-cancer activity was screened against two cancer cell lines in which compounds T2 and T3 were active against A549 cell lines and T6 was active against the HepG2 cell line. Stronger binding energy was found by comparing MM-PBSA simulations with molecular docking, which suggests that compounds T3 and T5 have a better possibility of being effective compounds, in which T5 showed higher binding affinity. The results suggest that these compounds have the potential to develop effective COX-2 inhibitors as anti-cancer agents.

4.
Life Sci ; 340: 122449, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38253310

RESUMO

AIMS: Cognitive impairment poses a considerable health challenge in the context of type 2 diabetes mellitus (T2DM), emphasizing the need for effective interventions. This study delves into the therapeutic efficacy of quercetin, a natural flavonoid, in mitigating cognitive impairment induced by T2DM in murine models. MATERIALS AND METHODS: Serum exosome samples were obtained from both T2DM-related and healthy mice for transcriptome sequencing, enabling the identification of differentially expressed mRNAs and long noncoding RNAs (lncRNAs). Subsequent experiments were conducted to ascertain the binding affinity between mmu-miR-129-5p, NEAT1 and BDNF. The structural characteristics and dimensions of isolated exosomes were scrutinized, and the expression levels of exosome-associated proteins were quantified. Primary mouse hippocampal neurons were cultured for in vitro validation, assessing the expression of pertinent genes as well as neuronal vitality, proliferation, and apoptosis capabilities. For in vivo validation, a T2DM mouse model was established, and quercetin treatment was administered. Changes in various parameters, cognitive ability, and the expression of insulin-related proteins, along with pivotal signaling pathways, were monitored. KEY FINDINGS: Analysis of serum exosomes from T2DM mice revealed dysregulation of NEAT1, mmu-miR-129-5p, and BDNF. In vitro investigations demonstrated that NEAT1 upregulated BDNF expression by inhibiting mmu-miR-129-5p. Overexpression of mmu-miR-129-5p or silencing NEAT1 resulted in the downregulation of insulin-related protein expression, enhanced apoptosis, and suppressed neuronal proliferation. In vivo studies validated that quercetin treatment significantly ameliorated T2DM-related cognitive impairment in mice. SIGNIFICANCE: These findings suggest that quercetin holds promise in inhibiting hippocampal neuron apoptosis and improving T2DM-related cognitive impairment by modulating the NEAT1/miR-129-5p/BDNF pathway within serum exosomes.


Assuntos
Disfunção Cognitiva , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Insulinas , MicroRNAs , RNA Longo não Codificante , Animais , Camundongos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Quercetina/farmacologia , Fator Neurotrófico Derivado do Encéfalo/genética , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Experimental/complicações , Proliferação de Células/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/genética
5.
Mol Cancer ; 22(1): 169, 2023 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-37814270

RESUMO

The use of nanotechnology has the potential to revolutionize the detection and treatment of cancer. Developments in protein engineering and materials science have led to the emergence of new nanoscale targeting techniques, which offer renewed hope for cancer patients. While several nanocarriers for medicinal purposes have been approved for human trials, only a few have been authorized for clinical use in targeting cancer cells. In this review, we analyze some of the authorized formulations and discuss the challenges of translating findings from the lab to the clinic. This study highlights the various nanocarriers and compounds that can be used for selective tumor targeting and the inherent difficulties in cancer therapy. Nanotechnology provides a promising platform for improving cancer detection and treatment in the future, but further research is needed to overcome the current limitations in clinical translation.


Assuntos
Nanopartículas , Neoplasias , Humanos , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Nanotecnologia/métodos , Sistemas de Liberação de Medicamentos/métodos , Portadores de Fármacos , Composição de Medicamentos
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