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1.
Cancer Metastasis Rev ; 43(1): 5-27, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37552389

RESUMO

The hypoxic environment is prominently witnessed in most solid tumors and is associated with the promotion of cell proliferation, epithelial-mesenchymal transition (EMT), angiogenesis, metabolic reprogramming, therapeutic resistance, and metastasis of tumor cells. All the effects are mediated by the expression of a transcription factor hypoxia-inducible factor-1α (HIF-1α). HIF-1α transcriptionally modulates the expression of genes responsible for all the aforementioned functions. The stability of HIF-1α is regulated by many proteins and non-coding RNAs (ncRNAs). In this article, we have critically discussed the crucial role of ncRNAs [such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), Piwi-interacting RNAs (piRNAs), and transfer RNA (tRNA)-derived small RNAs (tsRNAs)] in the regulation of stability and expression of HIF-1α. We have comprehensively discussed the molecular mechanisms and relationship of HIF-1α with each type of ncRNA in either promotion or repression of human cancers and therapeutic resistance. We have also elaborated on ncRNAs that are in clinical examination for the treatment of cancers. Overall, the majority of aspects concerning the relationship between HIF-1α and ncRNAs have been discussed in this article.


Assuntos
MicroRNAs , Neoplasias , Humanos , Proliferação de Células/genética , Resistencia a Medicamentos Antineoplásicos/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/genética , RNA não Traduzido/genética
2.
Exp Cell Res ; 442(2): 114236, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39245198

RESUMO

Widespread changes in the expression of microRNAs in cancer result in abnormal gene expression for the miRNAs that control those genes, which in turn causes changes to entire molecular networks and pathways. The frequently altered miR-31, which is found in a wide range of cancers, is one cancer-related miRNA that is particularly intriguing. MiR-31 has a very complicated set of biological functions, and depending on the type of tumor, it may act both as a tumor suppressor and an oncogene. The endogenous expression levels of miR-31 appear to be a key determinant of the phenotype brought on by aberrant expression. Varied expression levels of miR-31 could affect cell growth, metastasis, drug resistance, and other process by several mechanisms like targeting BRCA1-associated protein-1 (BAP1), large tumor suppressor kinase 1 (LATS1) and protein phosphatase 2 (PP2A). This review highlights the current understanding of the genes that miR-31 targets while summarizing the complex expression patterns of miR-31 in human cancers and the diverse phenotypes brought on by altered miR-31 expression.

3.
Toxicol Appl Pharmacol ; 490: 117037, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39004143

RESUMO

BACKGROUND: Fibromyalgia (FM) is a complex syndrome with somatic symptoms connected to the operational state of muscles. Although radiotherapy is a cornerstone in cancer treatment, it is implicated in the aggravation of FM. Lately, formulation of medicines in nano-forms become of great prominence due to their prospective applications in medicine. So, this study aimed to assess possible therapeutic benefits of formulating pregabalin in a nono-form (N-PG) for managing FM during exposure to gamma radiation. METHODS: Gamma rays administered in fractionated doses (2 Gy/day) to male rats after one hour of s.c. injection of reserpine (1 mL/kg per day) to induce FM, then treated with single daily dose of (30 mg/kg, p.o.) PG or N-PG for ten successive days. Rats were subjected to behavioral tests, then sacrificed to obtain serum and gastrocnemius muscles. RESULTS: N-PG significantly antagonized reserpine-induced FM as proved by; the immobility and performance times in forced swim and rotarod performance tests, respectively were restored near to the normal time, serum IL-8 and MCP-1 chemokines were nearby the normal levels, mitigated oxidative stress through increasing total thiol, Sirt3, CAT enzyme and decreasing COX-1, inhibition of inflammation via IL-1ß and MIF significant reduction, it possessed anti-apoptotic effect verified by decreasing PARP-1 and increasing Bcl-XL, gastrocnemius muscles had minimal fibrosis levels as seen after Masson trichrome staining. Histopathological results were coincidence with biochemical inspection. CONCLUSION: This study identifies N-PG as a novel drug that could be of a value in the management of FM particularly in cancer patients undergoing radiotherapy.


Assuntos
Fibromialgia , Raios gama , Interleucina-1beta , Músculo Esquelético , Ratos Wistar , Animais , Fibromialgia/tratamento farmacológico , Masculino , Interleucina-1beta/metabolismo , Ratos , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Músculo Esquelético/efeitos da radiação , Músculo Esquelético/patologia , Poli(ADP-Ribose) Polimerase-1/metabolismo , Modelos Animais de Doenças , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Nanopartículas
4.
Microb Cell Fact ; 23(1): 240, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39238019

RESUMO

Long-term antibiotic treatment results in the increasing resistance of bacteria to antimicrobials drugs, so it is necessary to search for effective alternatives to prevent and treat pathogens that cause diseases. This study is aimed for biological synthesis of silver Carthamus nanoparticles (Ag-Carth-NPs) to combat microbial biofilm formation and Pseudomonas aeruginosa virulence genes. Ag-Carth-NPs are synthesized using Carthamus tenuis aqueous extract as environmentally friendly method has no harmful effect on environment. General factorial design is used to optimize Ag-Carth-NPs synthesis using three variables in three levels are Carthamus extract concentration, silver nitrate concentration and gamma radiation doses. Analysis of response data indicates gamma radiation has a significant effect on Ag-Carth-NPs production. Ag-Carth-NPs have sharp peak at λ max 425 nm, small and spherical particles with size 20.0 ± 1.22 nm, high stability up to 240 day with zeta potential around - 43 ± 0.12 mV, face centered cubic crystalline structure and FT-IR spectroscopy shows peak around 620 cm-1 that corresponding to AgNPs that stabilized by C. tenuis extract functional moiety. The antibacterial activity of Ag-Carth-NPs against pathogenic bacteria and fungi was determined using well diffusion method. The MIC values of Ag-Carth-NPs were (6.25, 6.25, 3.126, 25, 12.5, 12.5, 25 and 12.5 µg/ml), MBC values were (12.5, 12.5, 6.25, 50, 25, 25, 50 and 25 µg/ml) and biofilm inhibition% were (62.12, 68.25, 90.12, 69.51, 70.61, 71.12, 75.51 and 77.71%) against Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Bacillus subtilis, Staphylococcus aureus, Staphylococcus epidermidis, Candida tropicalis and Candida albicans respectively. Ag-Carth-NPs has bactericidal efficacy and significantly reduced the swarming, swimming motility, pyocyanin and protease production of P. aeruginosa. Furthermore, P. aeruginosa ToxA gene expression was significantly down regulated by 81.5%, while exoU reduced by 78.1%, where lasR gene expression reduction was 68%, while the reduction in exoU was 66% and 60.1% decrease in lasB gene expression after treatment with Ag-Carth-NPs. This activity is attributed to effect of Ag-Carth-NPs on cell membrane integrity, down regulation of virulence gene expression, and induction of general and oxidative stress in P. aeruginosa. Ag-Carth-NPs have no significant cytotoxic effects on normal human cell (Hfb4) but have IC50 at 5.6µg/mL against of HepG-2 cells. Limitations of the study include studies with low risks of silver nanoparticles for in vitro antimicrobial effects and its toxicity.


Assuntos
Antibacterianos , Biofilmes , Nanopartículas Metálicas , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa , Prata , Biofilmes/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/genética , Nanopartículas Metálicas/química , Prata/farmacologia , Prata/química , Antibacterianos/farmacologia , Antibacterianos/química , Virulência/efeitos dos fármacos , Fatores de Virulência/genética , Fatores de Virulência/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética
5.
Helicobacter ; 29(4): e13110, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39001634

RESUMO

BACKGROUND: Antimicrobial-resistant Helicobacter pylori (H. pylori) poses a significant public health concern, especially given the limited therapeutic options for azithromycin-resistant strains. Hence, there is a necessity for new studies to reconsider the use of azithromycin, which has diminished in effectiveness against numerous strains. Thus, we aimed to augment azithromycin's anti-Helicobacter properties by combining it with curcumin in different formulations, including curcumin in clove oil, curcumin nano-gold emulsion, and curcumin nanoemulsion. METHODS: The antimicrobial activities of the investigated compounds, both individually and in combination with other anti-Helicobacter drugs, were evaluated. Their antibiofilm and anti-virulence properties were assessed using both phenotypic and genotypic methods, alongside molecular docking studies. Our findings were further validated through mouse protection assays and histopathological analysis. RESULTS: We observed high anti-Helicobacter activities of curcumin, especially curcumin nanoemulsion. A synergistic effect was detected between curcumin nanoemulsion and azithromycin with fraction inhibitory concentration index (FICI) values <0.5. The curcumin nanoemulsion was the most active anti-biofilm and anti-virulence compound among the examined substances. The biofilm-correlated virulence genes (babA and hopQ) and ureA genes were downregulated (fold change <1) post-treatment with curcumin nanoemulsion. On the protein level, the anti-virulence activities of curcumin nanoemulsion were documented based on molecular docking studies. These findings aligned with histopathological scoring of challenge mice, affirming the superior efficacy of curcumin nanoemulsion/azithromycin combination. CONCLUSION: The anti-Helicobacter activities of all curcumin physical forms pose significant challenges due to their higher  minimum inhibitory concentration (MIC) values exceeding the maximum permissible level. However, using curcumin nanoemulsion at sub-MIC levels could enhance the anti-Helicobacter activity of azithromycin and exhibit anti-virulence properties, thereby improving patient outcomes and addressing resistant pathogens. Therefore, more extensive studies are necessary to assess the safety of incorporating curcumin nanoemulsion into H. pylori treatment.


Assuntos
Antibacterianos , Azitromicina , Biofilmes , Curcumina , Infecções por Helicobacter , Simulação de Acoplamento Molecular , Azitromicina/farmacologia , Azitromicina/química , Animais , Antibacterianos/farmacologia , Antibacterianos/química , Camundongos , Biofilmes/efeitos dos fármacos , Curcumina/farmacologia , Curcumina/química , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/genética , Testes de Sensibilidade Microbiana , Sinergismo Farmacológico , Produtos Biológicos/farmacologia , Produtos Biológicos/química , Virulência/efeitos dos fármacos , Feminino
6.
Cell Biol Int ; 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39164963

RESUMO

This study explores the critical role of inhibitors targeting the mammalian target of rapamycin (mTOR) signaling pathway in breast cancer research and treatment. The mTOR pathway, a central regulator of cellular processes, has been identified as a crucial factor in the development and progression of breast cancer. The essay explains the complex molecular mechanisms through which mTOR inhibitors, such as rapamycin and its analogs, exert their anticancer effects. These inhibitors can stop cell growth, proliferation, and survival in breast cancer cells by blocking critical signaling pathways within the mTOR pathway. Furthermore, the essay discusses the implications of using mTOR inhibitors as a comprehensive therapeutic strategy. It emphasizes the potential benefits of combining mTOR inhibitors with other treatment approaches to enhance the effectiveness of breast cancer treatment. The evolving landscape of breast cancer research underscores the significance of mTOR as a therapeutic target and highlights ongoing efforts to improve and optimize mTOR inhibitors for clinical use. In conclusion, the essay asserts that inhibitors of the mTOR signaling pathway offer a promising approach in the fight against breast cancer. These inhibitors provide a focused and effective intervention targeting specific dysregulations within the mTOR pathway. As research advances, the integration of mTOR inhibitors into customized combination therapies holds excellent potential for shaping a more effective and personalized approach to breast cancer treatment, ultimately leading to improved outcomes for individuals affected by this complex and diverse disease.

7.
Mol Biol Rep ; 51(1): 964, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39240390

RESUMO

The intricate interplay between Homeobox genes, long non-coding RNAs (lncRNAs), and the development of malignancies represents a rapidly expanding area of research. Specific discernible lncRNAs have been discovered to adeptly regulate HOX gene expression in the context of cancer, providing fresh insights into the molecular mechanisms that govern cancer development and progression. An in-depth comprehension of these intricate associations may pave the way for innovative therapeutic strategies in cancer treatment. The HOX gene family is garnering increasing attention due to its involvement in immune system regulation, interaction with long non-coding RNAs, and tumor progression. Although initially recognized for its crucial role in embryonic development, this comprehensive exploration of the world of HOX genes contributes to our understanding of their diverse functions, potentially leading to immunology, developmental biology, and cancer research discoveries. Thus, the primary objective of this review is to delve into these aspects of HOX gene biology in greater detail, shedding light on their complex functions and potential therapeutic applications.


Assuntos
Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Genes Homeobox , Sistema Imunitário , Neoplasias , RNA Longo não Codificante , Humanos , Neoplasias/genética , Neoplasias/imunologia , RNA Longo não Codificante/genética , Genes Homeobox/genética , Sistema Imunitário/metabolismo , Animais
8.
J Biochem Mol Toxicol ; 38(6): e23719, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38764138

RESUMO

Cancer stem cells (CSCs) are associated with the tumor microenvironment (TME). CSCs induce tumorigenesis, tumor recurrence and progression, and resistance to standard therapies. Indeed, CSCs pose an increasing challenge to current cancer therapy due to their stemness or self-renewal properties. The molecular and cellular interactions between heterogeneous CSCs and surrounding TME components and tumor-supporting immune cells show synergistic effects toward treatment failure. In the immunosuppressive TME, CSCs express various immunoregulatory proteins, growth factors, metabolites and cytokines, and also produce exosomes, a type of extracellular vesicles, to protect themselves from host immune surveillance. Among these, the identification and application of CSC-derived exosomes could be considered for the development of therapeutic approaches to eliminate CSCs or cancer, in addition to targeting the modulators that remodel the composition of the TME, as reviewed in this study. Here, we introduce the role of CSCs and how their interaction with TME complicates immunotherapies, and then present the CSC-based immunotherapy and the limitation of these therapies. We describe the biology and role of tumor/CSC-derived exosomes that induce immune suppression in the TME, and finally, introduce their potentials for the development of CSC-based targeted immunotherapy in the future.


Assuntos
Células Dendríticas , Exossomos , Inibidores de Checkpoint Imunológico , Imunoterapia , Células-Tronco Neoplásicas , Microambiente Tumoral , Humanos , Exossomos/imunologia , Exossomos/metabolismo , Células-Tronco Neoplásicas/imunologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Imunoterapia/métodos , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Receptores de Antígenos Quiméricos/imunologia , Neoplasias/imunologia , Neoplasias/terapia , Vacinas Anticâncer/imunologia , Animais
9.
Artigo em Inglês | MEDLINE | ID: mdl-39279250

RESUMO

This study presents a novel approach to manage vaginal infections due to Candidiasis, utilizing a novel silver secnidazole nano-hybrid emulsion (Ag-Secn-NHE)-based probiotics and free Ag-Secn-NHE. Ag-Secn-NHE was prepared by simple homogenization‒ultrasonication technique and validated by using a ultraviolet‒visible scan, dynamic light scattering, transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy, and zeta potential. Saccharomyces cerevisiae (RCMB 002Y001) is the most effective probiotic-producing organism that demonstrates significant effects when combined with Ag-Secn-NHE. Ag-Secn-NHE-based probiotics showed significant antifungal effect compared to free Ag-Secn-NHE, silver nitrate, silver nanoparticles, secnidazole, secnidazole nanoemulsion, and commercial vaginal wash against multidrug-resistant vaginal pathogens. The highest inhibitory effect was achieved with Ag-Secn-NHE-based probiotic against Candida auris, Candida albicans, and Cryptococcus neoformans with minimal inhibitory concentration (MIC) 0.625 ± 0.002, 0.00625:1.25 ± 0.012 and 0.00625:1.25 ± 0.032 mg/mL, respectively, in comparison with Ag-Secn-NHE that show MIC at 0.00625:1.25 ± 0.612, 0.0125:2.5 ± 0.812, and 0.0125:2.5 ± 0.112 mg/mL (Ag:Secn). Ag-Secn-NHE-based- probiotic show minimum fungicidal concentration (MFC) at range from 2.5 to 20 mg/mL, wherever free Ag-Secn-NHE show MFC range from 5 to >20 mg/mL. Additionally, Ag-Secn-NHE-based probiotics have 75% inhibition of biofilm formation against C. auris and 60% inhibition of biofilm formation against both Cryptococcus neoformans and C. albicans in comparison with free Ag-Secn-NHE. Time-kill curves showed that the antifungal effect of Ag-Secn-NHE-based probiotics was fungistatic at 2MIC value after 4 h and after 16 h for Ag-Secn-NHE. TEM photographs showed that C. auris cells treated with Ag-Secn-NHE-based probiotic formula revealed severe deformations and distored ultrastructural changes. furthermore, results indicated that the Gamma radiation up to 15 kGy increases production of Ag-Secn-NHE in comparison with non-irradiated one.

10.
Cell Biochem Funct ; 42(4): e4029, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38773914

RESUMO

Mesenchymal stem cell-derived exosomes (MSC-Exos) are emerging as remarkable agents in the field of immunomodulation with vast potential for diagnosing and treating various diseases, including cancer and autoimmune disorders. These tiny vesicles are laden with a diverse cargo encompassing proteins, nucleic acids, lipids, and bioactive molecules, offering a wealth of biomarkers and therapeutic options. MSC-Exos exhibit their immunomodulatory prowess by skillfully regulating pattern-recognition receptors (PRRs). They conduct a symphony of immunological responses, modulating B-cell activities, polarizing macrophages toward anti-inflammatory phenotypes, and fine-tuning T-cell activity. These interactions have profound implications for precision medicine, cancer immunotherapy, autoimmune disease management, biomarker discovery, and regulatory approvals. MSC-Exos promises to usher in a new era of tailored therapies, personalized diagnostics, and more effective treatments for various medical conditions. As research advances, their transformative potential in healthcare becomes increasingly evident.


Assuntos
Exossomos , Células-Tronco Mesenquimais , Receptores de Reconhecimento de Padrão , Humanos , Exossomos/metabolismo , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/imunologia , Células-Tronco Mesenquimais/citologia , Receptores de Reconhecimento de Padrão/metabolismo , Animais , Imunomodulação
11.
Microb Pathog ; 176: 106020, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36746316

RESUMO

Recently in vivo and in vitro studies have provided evidence establishing the significance of microRNAs (miRNAs) in both physiological and pathological conditions. In this regard, the role of miRNA-128 (miR-128) in health and diseases has been found, and its critical regulatory role in the context of some viral diseases has been recently identified. For instance, it has been found that miR-128 can serve as an antiviral mediator and significantly limit the replication and dissemination of human immunodeficiency virus type 1 (HIV-1). Besides, it has been noted that poliovirus receptor-related 4 (PVRL4) is post-transcriptionally regulated by miR-128, representing possible miRNA targets that can modulate measles virus infection. Of note, the downregulation of seminal exosomes eca-miR-128 is associated with the long-term persistence of Equine arteritis virus (EAV) in the reproductive tract, and this particular miRNA is a putative regulator of chemokine ligand 16 (C-X-C motif) as determined by target prediction analysis. In this review, the latest information on the role and action mechanism of miR-128 in viral infections will be summarized and discussed in detail.


Assuntos
MicroRNAs , Viroses , Animais , Cavalos , Humanos , MicroRNAs/genética , Regulação para Baixo , Genitália , Replicação Viral
12.
Ecotoxicol Environ Saf ; 260: 115066, 2023 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-37262969

RESUMO

Membrane-based separation processes has been recently of significant global interest compared to other conventional separation approaches due to possessing undeniable advantages like superior performance, environmentally-benign nature and simplicity of application. Computational simulation of fluids has shown its undeniable role in modeling and simulation of numerous physical/chemical phenomena including chemical engineering, chemical reaction, aerodynamics, drug delivery and plasma physics. Definition of fluids can be occurred using the Navier-Stokes equations, but solving the equations remains an important challenge. In membrane-based separation processes, true perception of fluid's manner through disparate membrane modules is an important concern, which has been significantly limited applying numerical/computational procedures such s computational fluid dynamics (CFD). Despite this noteworthy advantage, the optimization of membrane processes using CFD is time-consuming and expensive. Therefore, combination of artificial intelligence (AI) and CFD can result in the creation of a promising hybrid model to accurately predict the model results and appropriately optimize membrane processes and phase separation. This paper aims to provide a comprehensive overview about the advantages of commonly-employed ML-based techniques in combination with the CFD to intelligently increase the optimization accuracy and predict mass transfer and the unfavorable events (i.e., fouling) in various membrane processes. To reach this objective, four principal strategies of AI including SL, USL, SSL and ANN were explained and their advantages/disadvantages were discussed. Then after, prevalent ML-based algorithm for membrane-based separation processes. Finally, the application potential of AI techniques in different membrane processes (i.e., fouling control, desalination and wastewater treatment) were presented.


Assuntos
Inteligência Artificial , Purificação da Água , Simulação por Computador , Algoritmos , Purificação da Água/métodos , Hidrodinâmica
13.
Pestic Biochem Physiol ; 197: 105701, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38072556

RESUMO

BACKGROUND: Aluminum phosphide (AlP) is a well-known toxic compound used as an agricultural pesticide to prevent insect damage to stored crops. However, even if just a small amount was consumed, it caused lasting harm to the human body and, in acute concentrations, death. The current study employed cerium oxide nanoparticles (CeO2 NPs) to reduce oxidative stress and various harmful outcomes of AlP poisoning. METHODS: Following finding effective concentrations of CeO2 NPs via MTT assay, Human Cardiac Myocyte (HCM) cells were pre-treated with CeO2 NPs for 24 h. After that, they were exposed to 2.36 µM AlP. The activity of oxidative stress and mitochondrial biomarkers, including mitochondrial swelling, mitochondrial membrane potential, and cytochrome c release, were evaluated in HCM cells. Finally, the population of apoptotic and necrotic cells was assessed via flow cytometry. RESULTS: After 24 h, data revealed that all tested concentrations of CeO2 NPs were safe, and 25 and 50 µM of that were selected as effective concentrations. Oxidative stress markers (malondialdehyde, protein carbonyl, superoxide dismutase, and catalase) showed that CeO2 NPs could successfully decrease AlP poisoning due to their antioxidant characteristics. Mitochondrial markers were also recovered by pre-treatment of HCM cells with CeO2 NPs. Furthermore, pre-treating with CeO2 NPs could compensate for the reduction of live cells with AlP and cause a diminishing in the population of early and late apoptotic cells. CONCLUSION: As a result, it is evident that CeO2 NPs, through the recovery of oxidative stress and mitochondrial damages caused by AlP, reduce apoptosis and have therapeutic potentials on HCM cells.


Assuntos
Nanopartículas , Praguicidas , Humanos , Praguicidas/toxicidade , Estresse Oxidativo
14.
World J Microbiol Biotechnol ; 39(12): 324, 2023 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-37773301

RESUMO

Helicobacter pylori (H. pylori) is the main cause of gastric diseases. However, the traditional antibiotic treatment of H. pylori is limited due to increased antibiotic resistance, low efficacy, and low drug concentration in the stomach. This study developed a Nano-emulsion system with ability to carry Curcumin and Clarithromycin to protect them against stomach acidity and increase their efficacy against H. pylori. We used oil in water emulsion system to prepare a novel Curcumin Clarithromycin Nano-Emulsion (Cur-CLR-NE). The nano-emulsion was validated by dynamic light scattering (DLS) technique, zeta potential; transmission electron microscopy (mean particle size 48 nm), UV-visible scanning and Fourier transform infrared spectroscopy (FT-IR). The in vitro assay of Cur-CLR-NE against H. pylori was evaluated by minimum inhibitory concentration (12.5 to 6.26 µg/mL), minimum bactericidal concentration (MBC) and anti-biofilm that showed a higher inhibitory effect of Cur-CLR-NE in compere with, free curcumin and clarithromycin against H. pylori. The in vivo results indicated that Cur-CLR-NE showed higher H. pylori clearance effect than free clarithromycin or curcumin under the same administration frequency and the same dose regimen. Histological analysis clearly showed that curcumin is highly effective in repairing damaged tissue. In addition, a potent synergistic effect was obvious between clarithromycin and curcumin in nano-emulsion system. The inflammation, superficial damage, the symptoms of gastritis including erosion in the mouse gastric mucosa, necrosis of the gastric epithelium gastric glands and interstitial oedema of tunica muscularis were observed in the positive control infected mice and absent from treated mice with Cur-CLR-NE.


Assuntos
Curcumina , Infecções por Helicobacter , Helicobacter pylori , Animais , Camundongos , Claritromicina/farmacologia , Claritromicina/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , Curcumina/farmacologia , Espectroscopia de Infravermelho com Transformada de Fourier , Antibacterianos/farmacologia , Testes de Sensibilidade Microbiana
15.
World J Microbiol Biotechnol ; 38(7): 119, 2022 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-35644864

RESUMO

Long-term antibiotic treatment results in the spread of multi-drug resistance in Pseudomonas aeruginosa that complicates treatment. Anti-virulence agents can be viewed as alternative options that cripple virulence factors of the bacteria to facilitate their elimination by the host immunity. The use of nanoparticles in the inhibition of P. aeruginosa virulence factors is a promising strategy. This study aims to study the effect of metformin (MET), metformin nano emulsions (MET-NEs), silver metformin nano emulsions (Ag-MET-NEs) and silver nanoparticles (AgNPs) on P. aeruginosa virulence factors' expression. The phenotypic results showed that MET-NEs had the highest virulence inhibitory activity. However, concerning RT-PCR results, all tested agents significantly decreased the expression of quorum sensing regulatory genes of P. aeruginosa; lasR, lasI, pqsA, fliC, exoS and pslA, with Ag-MET-NEs being the most potent one, however, it failed to protect mice from P. aeruginosa pathogenesis. MET-NEs showed the highest protective activity against pseudomonal infection in vivo. Our findings support the promising use of nano formulations particularly Ag-MET-NEs as an alternative against multidrug resistant pseudomonal infections via inhibition of virulence factors and quorum sensing gene expression.


Assuntos
Nanopartículas Metálicas , Metformina , Animais , Emulsões , Hipoglicemiantes/farmacologia , Metformina/farmacologia , Camundongos , Pseudomonas aeruginosa , Prata/farmacologia , Virulência , Fatores de Virulência/genética , Fatores de Virulência/metabolismo
16.
BMC Infect Dis ; 21(1): 149, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33546623

RESUMO

BACKGROUND: Lassa fever (LF) is a zoonotic infectious disease of public concern in Nigeria. The infection dynamics of the disease is not well elucidated in Nigeria. This study was carried out to describe the pattern of infection, case fatality rate and spread of lassa virus (LASV) from 2017 to 2020. METHODS: Weekly epidemiological data on LF from December, 2016 to September, 2020 were obtained from Nigeria Centre for Disease Control. The number of confirmed cases and deaths were computed according to months and states. Descriptive statistics was performed and case fatality rate was calculated. Distribution and spread maps of LF over the four years period was performed on ArcMap 10.7. RESULTS: A total of 2787 confirmed cases and 516 deaths were reported in Nigeria from December, 2016 to September, 2020. Increase in number of cases and deaths were observed with 298, 528, 796 and 1165 confirmed cases and 79, 125, 158 and 158 deaths in 2017, 2018, 2019 and 2020 respectively. Over 60% of the cases were reported in two states, Edo and Ondo states. The LF cases spread from 19 states in 2017 to 32 states and Federal Capital Territory (FCT) in 2020. Ondo state (25.39%) had the highest of deaths rate from LF over the four years. Case fatality rate (CFR) of LF was highest in 2017 (26.5%) with CFR of 23.7, 19.6 and 13.4% in 2018, 2019 and 2020 respectively. The peak of infection was in the month of February for the four years. Infections increases at the onset of dry season in November and decline till April when the wet season sets-in. CONCLUSION: There is an annual increase in the number of LASV infection across the states in Nigeria. There is need to heighten control strategies through the use of integrated approach, ranging from vector control, health education and early diagnosis.


Assuntos
Febre Lassa/mortalidade , Febre Lassa/transmissão , Animais , Geografia , Humanos , Febre Lassa/epidemiologia , Vírus Lassa , Mortalidade/tendências , Nigéria/epidemiologia , Estações do Ano , Zoonoses/epidemiologia , Zoonoses/mortalidade , Zoonoses/transmissão
17.
Biometals ; 34(4): 815-829, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33895912

RESUMO

Aqueous glutathione selenium nano-incorporation (GSH-SeN-Inco) was prepared by gamma radiation in presence of microbial glutathione (GSH) and selenium dioxide. The novel prepared GSH-SeN-Inco are validated by UV-vis spectroscopy, TEM (17.5 nm), DLS, XRD, EDX and FTIR spectrum reveals the presence of GSH moiety that coating the selenium nanoparticles (SeNPs) forming GSH-SeN-Inco. The XRD analysis verified the presence of metallic SeNPs. The nucleation and radiolysis mechanism of GSH-SeN-Inco formation are also discussed. The size GSH-SeN-Inco (17.5 nm) is affected by certain factors such as concentration of GSH, selenium dioxide, and absorbed dose of gamma radiation. The present study explored the positive role of GSH-SeN-Inco as an antitumor activity against HepG-2 and MCF-7, with IC50 at a concentration of 1.00 and 0.9 mM, respectively. The GSH-SeN-Inco show significant scavenging activity at 33%. The GSH-SeN-Inco shows antimicrobial potential against Gram-negative and Gram-positive bacteria with significant MIC especially Escherichia coli ATCC 25922 at 5.20 µg/ml.


Assuntos
Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Glutationa/farmacologia , Nanopartículas/química , Selênio/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Antineoplásicos/síntese química , Antineoplásicos/química , Antioxidantes/síntese química , Antioxidantes/química , Compostos de Bifenilo/antagonistas & inibidores , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Glutationa/química , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Humanos , Tamanho da Partícula , Picratos/antagonistas & inibidores , Selênio/química
18.
Molecules ; 26(16)2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34443593

RESUMO

Curcuma longa is very well-known medicinal plant not only in the Asian hemisphere but also known across the globe for its therapeutic and medicinal benefits. The active moiety of Curcuma longa is curcumin and has gained importance in various treatments of various disorders such as antibacterial, antiprotozoal, cancer, obesity, diabetics and wound healing applications. Several techniques had been exploited as reported by researchers for increasing the therapeutic potential and its pharmacological activity. Here, the dictum is the new room for the development of physicochemical, as well as biological, studies for the efficacy in target specificity. Here, we discussed nanoformulation techniques, which lend support to upgrade the characters to the curcumin such as enhancing bioavailability, increasing solubility, modifying metabolisms, and target specificity, prolonged circulation, enhanced permeation. Our manuscript tried to seek the attention of the researcher by framing some solutions of some existing troubleshoots of this bioactive component for enhanced applications and making the formulations feasible at an industrial production scale. This manuscript focuses on recent inventions as well, which can further be implemented at the community level.


Assuntos
Curcumina/química , Curcumina/uso terapêutico , Terapia de Alvo Molecular/métodos , Nanomedicina/métodos , Nanopartículas , Animais , Humanos
19.
Biomed Chromatogr ; 34(7): e4836, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32222076

RESUMO

The dissipation dynamic and residues of spiroxamine in open-field-grown strawberries were determined using liquid chromatography tandem mass spectrometry (LC-MS/MS). Spiroxamine application was performed according to Egyptian good agricultural practices recommendation. A QuEChERS-based extraction method along with direct analysis with an LC-MS/MS analytical method were optimized and validated, and the specificity of the techniques used was considered satisfactory. Good linearity (R2 > 0.999) was obtained for spiroxamine within the range of 0.001-0.1 µg/ml. The mean recoveries varied between 97.1 and 108.2%, with inter- and intra-day precision (RSD) <4.9%. The limit of quantitation for spiroxamine was 0.001 mg/kg. The results indicated that spiroxamine degradation in strawberry followed first-order kinetics (R2 > 0.9929) with an estimated half-life value of 4.71 days. Considering the Australian maximum residue limit (0.05 mg/kg) in strawberry and based on the results from residue trials with a preharvest interval of 14 days for strawberry, compliance can be expected. The present results could provide guidance to fully evaluate the risks of spiroxamine residues, preventing any potential health risk to consumers.


Assuntos
Cromatografia Líquida/métodos , Fragaria , Fungicidas Industriais/análise , Resíduos de Praguicidas/análise , Compostos de Espiro/análise , Egito , Inocuidade dos Alimentos , Fragaria/química , Fragaria/metabolismo , Fungicidas Industriais/farmacocinética , Modelos Lineares , Resíduos de Praguicidas/farmacocinética , Reprodutibilidade dos Testes , Medição de Risco , Sensibilidade e Especificidade , Compostos de Espiro/farmacocinética , Espectrometria de Massas em Tandem/métodos
20.
Public Health ; 176: 172-180, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29666024

RESUMO

OBJECTIVE: In Canada, indigenous peoples suffer from a multitude of health disparities. To better understand these disparities, this study aims to examine the social determinants of self-reported health for indigenous peoples in Canada. STUDY DESIGN: This study uses data from Statistics Canada's Aboriginal Peoples Survey 2012. METHODS: Multinomial logistic regression models were used to examine how selected social determinants of health are associated with self-reported health among off-reserve First Nations and Métis peoples in Canada. RESULTS: Our analysis shows that being older, female, and living in urban settings were significantly associated with negative ratings of self-reported health status among the indigenous respondents. Additionally, we found that higher income and levels of education were strongly and significantly associated with positive ratings of self-reported health status. Compared with indigenous peoples with an education level of grade 8 or lower, respondents with higher education were 10 times (5.35-22.48) more likely to report 'excellent' and 'very good' health. Respondents who earned more than $40,000 annually were three times (2.17-4.72) more likely to report 'excellent' and 'very good' health compared with those who earned less than $20,000 annually. When interacted with income, we also found that volunteering in the community is associated with better self-reported health. CONCLUSIONS: There are known protective determinants (income and education) and risk determinants (location of residence, gender, and age) which are associated with self-reported health status among off-reserve First Nations and Métis peoples. For indigenous-specific determinants, volunteering in the community appears to be associated with self-perceived health status. Thus, addressing these determinants will be necessary to achieve better health outcomes for indigenous peoples in Canada. Next steps include developing indigenous-specific social determinants of health indicators that adequately measure culture, connection, and community.


Assuntos
Indígenas Norte-Americanos/estatística & dados numéricos , Determinantes Sociais da Saúde/etnologia , Adulto , Canadá , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prática de Saúde Pública , Autorrelato , Fatores Socioeconômicos , Inquéritos e Questionários , Adulto Jovem
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