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1.
FASEB J ; 38(4): e23480, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38354025

RESUMO

Accumulating evidence suggests that dysregulation of FOXO3a plays a significant role in the progression of various malignancies, including hepatocellular carcinoma (HCC). FOXO3a inactivation, driven by oncogenic stimuli, can lead to abnormal cell growth, suppression of apoptosis, and resistance to anticancer drugs. Therefore, FOXO3a emerges as a potential molecular target for the development of innovative treatments in the era of oncology. Linagliptin (LNGTN), a DPP-4 inhibitor known for its safe profile, has exhibited noteworthy anti-inflammatory and anti-oxidative properties in previous in vivo studies. Several potential molecular mechanisms have been proposed to explain these effects. However, the capacity of LNGTN to activate FOXO3a through AMPK activation has not been investigated. In our investigation, we examined the potential repurposing of LNGTN as a hepatoprotective agent against diethylnitrosamine (DENA) intoxication. Additionally, we assessed LNGTN's impact on apoptosis and autophagy. Following a 10-week administration of DENA, the liver underwent damage marked by inflammation and early neoplastic alterations. Our study presents the first experimental evidence demonstrating that LNGTN can reinstate the aberrantly regulated FOXO3a activity by elevating the nuclear fraction of FOXO3a in comparison to the cytosolic fraction, subsequent to AMPK activation. Moreover, noteworthy inactivation of NFκB induced by LNGTN was observed. These effects culminated in the initiation of apoptosis, the activation of autophagy, and the manifestation of anti-inflammatory, antiproliferative, and antiangiogenic outcomes. These effects were concomitant with improved liver function and microstructure. In conclusion, our findings open new avenues for the development of novel therapeutic strategies targeting the AMPK/FOXO3a signaling pathway in the management of chronic liver damage.


Assuntos
Carcinoma Hepatocelular , Inibidores da Dipeptidil Peptidase IV , Neoplasias Hepáticas , Animais , Ratos , Linagliptina/farmacologia , Proteínas Quinases Ativadas por AMP , Dietilnitrosamina/toxicidade , Carcinoma Hepatocelular/induzido quimicamente , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/induzido quimicamente , Neoplasias Hepáticas/tratamento farmacológico , Hipoglicemiantes , Inibidores de Proteases , Antivirais , Anti-Inflamatórios
2.
Exp Cell Res ; 442(2): 114279, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39389336

RESUMO

Pituitary adenomas (PAs) are an array of tumors originating from the pituitary gland. PAs are sorted as functional or nonfunctional according to their hormonal activity and classified according to size into microadenomas and macroadenomas. Still, the cellular events that trigger the transformations in pituitary neoplasms are not fully understood, and the current classification methods do not precisely predict clinical behavior. A rising number of researches have emphasized the role of miRNAs, that drawn more attention as oncogenic molecules or tumor suppressors. The etiopathological mechanisms of PAs include multiple molecular cascades that are influenced by different miRNAs. miRNAs control the cell cycle control, pro- or antiapoptotic processes, and tumor invasion and metastasis. miRNAs offer a novel perspective on tumor features and behaviors and might be valuable in prognostication and therapeutic plans. In pituitary adenomas, miRNAs showed a specific expression pattern depending on their size, cell origin, remission, and treatments. Screening miRNA expression patterns is promising to monitor and evaluate recurrence, as well as to investigate the efficacy of radiation and chemotherapy for PAs exhibiting aggressive behavior. Thus, the current review investigated the interplay of the miRNAs' pivotal role in offering new opportunities to translate these innovative epigenetic tools into healthcare applications.


Assuntos
Adenoma , Regulação Neoplásica da Expressão Gênica , MicroRNAs , Neoplasias Hipofisárias , Humanos , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/patologia , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/metabolismo , MicroRNAs/genética , Adenoma/genética , Adenoma/patologia , Adenoma/diagnóstico , Adenoma/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Animais
3.
Exp Cell Res ; 442(2): 114234, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39233267

RESUMO

MicroRNAs (miRNAs), which are non-coding RNAs consisting of 18-24 nucleotides, play a crucial role in the regulatory pathways of inflammatory diseases. Several recent investigations have examined the potential role of miRNAs in forming Crohn's disease (CD). It has been suggested that miRNAs serve as diagnostics for both fibrosis and inflammation in CD due to their involvement in the mechanisms of CD aggravation and fibrogenesis. More information on CD pathophysiology could be obtained by identifying the miRNAs concerned with CD and their target genes. These findings have prompted several in vitro and in vivo investigations into the putative function of miRNAs in CD treatment. Although there are still many unanswered questions, the growing body of evidence has brought miRNA-based therapy one step closer to clinical practice. This extensive narrative study offers a concise summary of the most current advancements in CD. We go over what is known about the diagnostic and therapeutic benefits of miRNA mimicry and inhibition so far, and we see what additional miRNA family targets could be useful for treating CD-related inflammation and fibrosis.


Assuntos
Doença de Crohn , MicroRNAs , Doença de Crohn/genética , Doença de Crohn/terapia , Doença de Crohn/patologia , MicroRNAs/genética , Humanos , Animais , Inflamação/genética , Fibrose/genética
4.
Curr Atheroscler Rep ; 26(8): 395-410, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38869707

RESUMO

PURPOSE OF REVIEW: To eradicate atherosclerotic diseases, novel biomarkers, and future therapy targets must reveal the burden of early atherosclerosis (AS), which occurs before life-threatening unstable plaques form. The chemical and biological features of microRNAs (miRNAs) make them interesting biomarkers for numerous diseases. We summarized the latest research on miRNA regulatory mechanisms in AS progression studies, which may help us use miRNAs as biomarkers and treatments for difficult-to-treat diseases. RECENT FINDINGS: Recent research has demonstrated that miRNAs have a regulatory function in the observed changes in gene and protein expression during atherogenesis, the process that leads to atherosclerosis. Several miRNAs play a role in the development of atherosclerosis, and these miRNAs could potentially serve as non-invasive biomarkers for atherosclerosis in various regions of the body. These miRNAs have the potential to serve as biomarkers and targets for early treatment of atherosclerosis. The start and development of AS require different miRNAs. It reviews new research on miRNAs affecting endothelium, vascular smooth muscle, vascular inflammation, lipid retention, and cholesterol metabolism in AS. A miRNA gene expression profile circulates with AS everywhere. AS therapies include lipid metabolism, inflammation reduction, and oxidative stress inhibition. Clinical use of miRNAs requires tremendous progress. We think tiny miRNAs can enable personalized treatment.


Assuntos
Aterosclerose , Biomarcadores , MicroRNAs , Humanos , Aterosclerose/genética , Aterosclerose/metabolismo , Aterosclerose/diagnóstico , Aterosclerose/terapia , MicroRNAs/genética , MicroRNAs/metabolismo , Biomarcadores/metabolismo , Prognóstico , Animais
5.
Molecules ; 28(15)2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37570781

RESUMO

In the current study, clove oil nanoemulsion (CL-nanoemulsion) and emulsion (CL-emulsion) were prepared through an ecofriendly method. The prepared CL-nanoemulsion and CL-emulsion were characterized using dynamic light scattering (DLS) and a transmission electron microscope (TEM), where results illustrated that CL-nanoemulsion droplets were approximately 32.67 nm in size and spherical in shape, while CL-nanoemulsion droplets were approximately 225.8 nm with a spherical shape. The antibacterial activity of CL-nanoemulsion and CL-emulsion was carried out using a microbroth dilution method. Results revealed that the preferred CL-nanoemulsion had minimal MIC values between 0.31 and 5 mg/mL. The antibiofilm efficacy of CL-nanoemulsion against S. aureus significantly decreased the development of biofilm compared with CL-emulsion. Furthermore, results illustrated that CL-nanoemulsion showed antifungal activity significantly higher than CL-emulsion. Moreover, the prepared CL-nanoemulsion exhibited outstanding antifungal efficiency toward Candida albicans, Cryptococcus neoformans, Aspergillus brasiliensis, A. flavus, and A. fumigatus where MICs were 12.5, 3.12, 0.78, 1.56, and 1.56 mg/mL, respectively. Additionally, the prepared CL-nanoemulsion was analyzed for its antineoplastic effects through a modified MTT assay for evaluating apoptotic and cytotoxic effects using HepG2 and MCF-7 cell lines. MCF-7 breast cancer cells showed the lowest IC50 values (3.4-fold) in CL-nanoemulsion relative to that of CL-emulsion. Thus, CL-nanoemulsion induces apoptosis in breast cancer cells by inducing caspase-8 and -9 activity and suppressing VEGFR-2. In conclusion, the prepared CL-nanoemulsion had antibacterial, antifungal, and antibiofilm as well as anticancer properties, which can be used in different biomedical applications after extensive studies in vivo.


Assuntos
Antibacterianos , Antifúngicos , Antineoplásicos , Biofilmes , Óleos Voláteis , Syzygium , Biofilmes/efeitos dos fármacos , Antineoplásicos/química , Antineoplásicos/farmacologia , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Emulsões , Syzygium/química , Difusão Dinâmica da Luz , Microscopia Eletrônica de Transmissão , Células Hep G2 , Células MCF-7 , Humanos , Apoptose , Antibacterianos/química , Antibacterianos/farmacologia , Antifúngicos/química , Antifúngicos/farmacologia , Sistemas de Liberação de Fármacos por Nanopartículas , Nanoestruturas/química , Staphylococcus aureus/efeitos dos fármacos , Fungos/efeitos dos fármacos
6.
Pharm Biol ; 60(1): 2134-2144, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36305518

RESUMO

CONTEXT: Chitosan is a biocompatible polysaccharide that has been widely exploited in biomedical and drug delivery applications. OBJECTIVE: This study explores the renoprotective effect of chitosan nanoparticles in vivo in rats. MATERIALS AND METHODS: Chitosan nanoparticles were prepared via ionotropic gelation method, and several in vitro characterizations were performed, including measurements of particle size, zeta potential, polydispersity index, Fourier transform-infrared spectroscopy, differential scanning calorimetry, and transmission electron microscopy (TEM) imaging. Wistar rats were divided randomly into four groups; negative control, CCl4-induced nephrotoxicity (untreated), and two groups receiving CCl4 + chitosan NPs (10 and 20 mg/kg) orally for 2 weeks. The renoprotective effect was assessed by measuring oxidative, apoptotic, and inflammatory biomarkers, and via histopathological and immunohistochemical examinations for the visualization of NF-κB and COX-2 in renal tissues. RESULTS: Monodisperse spherical nanosized (56 nm) particles were successfully prepared as evidenced by dynamic light scattering and TEM. Oral administration of chitosan nanoparticles (10 and 20 mg/kg) concurrently with CCl4 for 2 weeks resulted in 13.6% and 21.5% reduction in serum creatinine and increase in the level of depleted reduced glutathione (23.1% and 31.8%), respectively, when compared with the positive control group. Chitosan nanoparticles (20 mg/kg) revealed a significant (p ˂ 0.05) decrease in malondialdehyde levels (30.6%), tumour necrosis factor-α (33.6%), interleukin-1ß (31.1%), and caspase-3 (36.6%). CONCLUSIONS: Chitosan nanoparticles afforded significant protection and amelioration against CCl4-induced nephrotoxicity. Thus, chitosan nanoparticles could afford a potential nanotherapeutic system for the management of nephrotoxicity which allows for broadening their role in biomedical delivery applications.


Assuntos
Quitosana , Nanopartículas , Animais , Ratos , Quitosana/química , Ratos Wistar , Tetracloreto de Carbono/toxicidade , Tamanho da Partícula
7.
Pharm Res ; 38(11): 1821-1838, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34853982

RESUMO

AIMS: Gastric ulcer is a continuous worldwide threat that inquires protective agents. Olmesartan (OLM) has potent anti-oxidant and anti-inflammatory characters, yet having limited bioavailability. We targeted the gastro-protective potential and probable mechanism of OLM and its niosomal form against indomethacin (IND) induced-gastric ulcer in rats. MAIN METHODS: we prepared OLM niosomes (OLM-NIO) with different surfactant: cholesterol molar ratios. We evaluated particle size, zeta-potential, polydispersity, and entrapment efficiency. In-vitro release study, Fourier transform infrared spectroscopy, differential scanning calorimetry, and transmission electron microscopy were performed for selected niosomes. In-vivo, we used oral Omeprazole (30 mg/kg), OLM or OLM-NIO (10 mg/kg) for 3 days before IND (25 mg/kg) ingestion. We assessed gastric lesions, oxidative and inflammatory markers. KEY FINDINGS: OLM-NIO prepared with span 60:cholesterol ratio (1:1) showed high entrapment efficiency 93 ± 2%, small particle size 159.3 ± 6.8 nm, low polydispersity 0.229 ± 0.009, and high zeta-potential -35.3 ± 1.2 mV, with sustained release mechanism by release data. In-vivo macroscopical and histological results showed gastro-protective effects of OLM pretreatment, which improved oxidative stress parameters and enhanced the gastric mucosal cyclooxygenase-1 (COX-1) and prostaglandin E2 (PGE2) contents. OLM pretreatment suppressed interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) contents and translocation of p38 mitogen-activated protein kinase (p38-MAPK). Besides, OLM substantially promoted the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) protective pathway. OLM-NIO furtherly improved all previous outcomes. SIGNIFICANCE: We explored OLM anti-ulcerative effects, implicating oxidative stress and inflammation improvement, mediated by the Nrf2/HO-1 signaling pathway and p38-MAPK translocation. Meanwhile, the more bioavailable OLM-NIO achieved better gastro-protective effects compared to conventional OLM form.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/administração & dosagem , Anti-Inflamatórios não Esteroides/efeitos adversos , Imidazóis/administração & dosagem , Indometacina/efeitos adversos , Úlcera Gástrica/tratamento farmacológico , Tetrazóis/administração & dosagem , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacocinética , Animais , Disponibilidade Biológica , Modelos Animais de Doenças , Liberação Controlada de Fármacos , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/patologia , Heme Oxigenase (Desciclizante)/metabolismo , Humanos , Imidazóis/farmacocinética , Lipossomos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Fator 2 Relacionado a NF-E2/metabolismo , Ratos , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/patologia , Tetrazóis/farmacocinética
8.
Artigo em Inglês | MEDLINE | ID: mdl-39453501

RESUMO

Diabetes mellitus (DM) is a persistent condition characterized by high levels of glucose in the blood due to irregularities in the secretion of insulin, its action, or both. The disease was believed to be incurable until insulin was extracted, refined, and produced for sale. In DM, insulin delivery devices and insulin analogs have improved glycemic management even further. Sulfonylureas, biguanides, alpha-glucosidase inhibitors, and thiazolidinediones are examples of newer-generation medications having high efficacy in decreasing hyperglycemia as a result of scientific and technological advancements. Incretin mimetics, dual glucose-dependent insulinotropic polypeptide, GLP-1 agonists, PPARs, dipeptidyl peptidase-4 inhibitors, anti-CD3 mAbs, glucokinase activators, and glimins as targets have all performed well in recent clinical studies. Considerable focus was placed on free FA receptor 1 agonist, protein tyrosine phosphatase-1B inhibitors, and Sparc-related modular calcium-binding protein 1 which are still being studied. Theranostics, stem cell therapy, gene therapy, siRNA, and nanotechnology are some of the new therapeutic techniques. Traditional Chinese medicinal plants will also be discussed. This study seeks to present a comprehensive analysis of the latest research advancements, the emerging trends in medication therapy, and the utilization of delivery systems in treating DM. The objective is to provide valuable insights into the application of different pharmaceuticals in the field of diabetes mellitus treatment. Also, the therapeutic approach for diabetic patients infected with COVID-19 will be highlighted. Recent clinical and experimental studies evidence the Egyptian experience. Finally, as per the knowledge of the state of the art, our conclusion and future perspective will be declared.

9.
Int J Biol Macromol ; 260(Pt 1): 129323, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38242393

RESUMO

Currently, there are no viable curative treatments that can enhance the central nervous system's (CNS) recovery from trauma or illness. Bioengineered injectable smart/stimuli-responsive hydrogels (SSRHs) that mirror the intricacy of the CNS milieu and architecture have been suggested as a way to get around these restrictions in combination with medication and cell therapy. Additionally, the right biophysical and pharmacological stimuli are required to boost meaningful CNS regeneration. Recent research has focused heavily on developing SSRHs as cutting-edge delivery systems that can direct the regeneration of brain tissue. In the present article, we have discussed the pathology of brain injuries, and the applicable strategies employed to regenerate the brain tissues. Moreover, the most promising SSRHs for neural tissue engineering (TE) including alginate (Alg.), hyaluronic acid (HA), chitosan (CH), gelatin, and collagen are used in natural polymer-based hydrogels and thoroughly discussed in this review. The ability of these hydrogels to distribute bioactive substances or cells in response to internal and external stimuli is highlighted with particular attention. In addition, this article provides a summary of the most cutting-edge techniques for CNS recovery employing SSRHs for several neurodegenerative diseases.


Assuntos
Quitosana , Engenharia Tecidual , Engenharia Tecidual/métodos , Gelatina , Hidrogéis/farmacologia , Polímeros , Encéfalo
10.
Biomater Sci ; 2024 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-39484700

RESUMO

Lipid nanoparticles (LNPs) have emerged as transformative tools in modern drug delivery, offering unparalleled potential in enhancing the efficacy and safety of various therapeutics. In the context of rheumatoid arthritis (RA), a disabling autoimmune disorder characterized by chronic inflammation, joint damage, and limited patient mobility, LNPs hold significant promise for revolutionizing treatment strategies. LNPs offer several advantages over traditional drug delivery systems, including improved pharmacokinetics, enhanced tissue penetration, and reduced systemic toxicity. This article concisely summarizes the pathogenesis of RA, its associated risk factors, and therapeutic techniques and their challenges. Additionally, it highlights the noteworthy advancements made in managing RA through LNPs, including liposomes, niosomes, bilosomes, cubosomes, spanlastics, ethosomes, solid lipid nanoparticles, lipid micelles, lipid nanocapsules, nanostructured lipid carriers, etc. It also delves into the specific functional attributes of these nanocarrier systems, focusing on their role in treating and monitoring RA.

11.
Eur J Pharm Biopharm ; 200: 114324, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38759898

RESUMO

This study introduces two innovative nanocarrier systems to improve oral drug delivery. Desosomes and desimicelles combine Deep eutectic solvent (DES) with vesicular or micellar nanosystems, respectively. These novel nanosystems integrate the DES solubilization potency for administering drugs with low aqueous solubility and the vesicular and micellar systems to bypass physiological barriers and improve poor drug bioavailability. Lornoxicam (LRX) is a BCS class II anti-inflammatory with limited aqueous solubility and rapid clearance. Desosomes and desimicelles were prepared and successfully optimized. The optimization depended on particle size, zetapotential, entrapment efficiency, and solubility. The optimized desosomes (LRX-DES-V) and desimicelles (LRX-DES-M) were pictured by transmission electron microscope. Differential scanning calorimetry (DSC) and FTIR analysis indicated the successful inclusion of LRX inside each system. Invitro LRX release profiles revealed controlled release of LRX-DES-V and LRX-DES-M, with more sustained release by the later one. In-vivo study, inflammation was induced using a carrageenan rat model, and the anti-inflammatory effect of LRX-pure, marketed product, traditional niosomes, LRX-DES-V & LRX-DES-M were determined using inhibition %, serum inflammatory cytokines, and histopathology. After 4 h of induction, LRX-DES-M (68.05%) showed a significant inhibition compared to LRX-DES-V (63.57%). LRX-DES-M also showed a better reduction in COX2, PGE2, and TNF-α (1.25-fold, 1.24-fold, and 1.36-fold inhibition), respectively, compared to LRX-DES-V. We can conclude that LRX-DES-V and LRX-DES-M showed better effects than all other groups and that LRX-DES-M might be more effective than LRX-DES-V.


Assuntos
Micelas , Tamanho da Partícula , Piroxicam , Solubilidade , Animais , Ratos , Administração Oral , Piroxicam/administração & dosagem , Piroxicam/farmacocinética , Piroxicam/análogos & derivados , Piroxicam/química , Masculino , Sistemas de Liberação de Medicamentos/métodos , Portadores de Fármacos/química , Disponibilidade Biológica , Liberação Controlada de Fármacos , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/farmacocinética , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/química , Lipossomos , Ratos Wistar , Nanopartículas/química , Solventes/química , Carragenina , Varredura Diferencial de Calorimetria
12.
Med Oncol ; 41(9): 232, 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39167288

RESUMO

The clinical studies for breast cancer (BC) are now assessing the efficacy of 2-Methoxyestradiol (2-ME), a naturally occurring derivative of estradiol. Our study aimed to explore the potential of combining the 2-ME and tamoxifen (TAM) on sensitization of TAM-resistant cells using LCC2 the TAM-resistant cells as a model and comparing the results to the sensitive cells MCF-7. Sulphorhodamine-B (SRB) assay is used to examine the 2-ME chemo-sensitizing impact on the cytotoxicity of TAM on LCC2 cells. Colorimetric assay kits were used to assess the level of the apoptosis-related markers caspases 3, Bcl2, and Bax in cell lysate. Hypoxia-inducible factor 1 alpha (HIF-1α) expression was measured using western blotting. Total cholesterol and triglyceride (TG) levels were examined colorimetrically, using the BIOLABO kit. The use of 2-ME enhanced the cytotoxic effects of TAM and effectively reversed TAM resistance. This was achieved by inhibiting the expression of HIF-1α, while concurrently increasing the levels of apoptotic marker caspase-3, as well as the pro-apoptotic protein Bax. Additionally, there was a reduction in the levels of Bcl2, an anti-apoptotic protein. Furthermore, a reduction in TG and cholesterol levels was noted. Our findings show that HIF-1α plays an important role in TAM resistance and that suppression of HIF-1α by 2-ME-mediated sensitization of BC-resistant cells to TAM. Therefore, the concurrent administration of TAM/2-ME might potentially serve as a viable therapeutic approach to address TAM resistance and enhance the overall therapy efficacy for patients with BC.


Assuntos
2-Metoxiestradiol , Neoplasias da Mama , Regulação para Baixo , Resistencia a Medicamentos Antineoplásicos , Subunidade alfa do Fator 1 Induzível por Hipóxia , Tamoxifeno , Humanos , 2-Metoxiestradiol/farmacologia , Tamoxifeno/farmacologia , Tamoxifeno/análogos & derivados , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Células MCF-7 , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Feminino , Regulação para Baixo/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Antineoplásicos Hormonais/farmacologia , Estradiol/farmacologia , Estradiol/análogos & derivados
13.
Pathol Res Pract ; 253: 155093, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38184962

RESUMO

Stroke is a widespread neurological disorder associated with physical disabilities, mortality, and economic burden. In recent decades, substantial progress has been achieved in reducing the impact of this public health problem. However, further understanding of the pathophysiology of stroke and the underlying genetic pathways is required. The pathological mechanisms of stroke comprise multifaceted molecular cascades regulated by various microRNAs (miRNAs). An increasing number of studies have highlighted the role of miRNAs, which have received much attention during the last decades as an important class of post-transcriptional regulators. It was shown that miRNAs exert their role in the etiology of stroke via mediating excitotoxicity and neuroinflammation. Additionally, miRNAs could be helpful as non-invasive or minimally invasive biomarkers and therapeutic agents. Thus, the current review focused on the interplay of these miRNAs in stroke pathology to upgrade the existing therapeutic strategies.


Assuntos
MicroRNAs , Acidente Vascular Cerebral , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Doenças Neuroinflamatórias , Acidente Vascular Cerebral/genética , Acidente Vascular Cerebral/terapia , Biomarcadores/metabolismo
14.
Eur J Pharm Biopharm ; 196: 114205, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38311187

RESUMO

The targeting and mucoadhesive features of chitosan (CS)-linked solid lipid nanoparticles (SLNs) were exploited to efficiently deliver fexofenadine (FEX) into the colon, forming a novel and potential oral therapeutic option for ulcerative colitis (UC) treatment. Different FEX-CS-SLNs with varied molecular weights of CS were prepared and optimized. Optimized FEX-CS-SLNs exhibited 229 ± 6.08 nm nanometric size, 36.3 ± 3.18 mV zeta potential, 64.9 % EE, and a controlled release profile. FTIR, DSC, and TEM confirmed good drug entrapment and spherical particles. Mucoadhesive properties of FEX-CS-SLNs were investigated through mucin incubation and exhibited considerable mucoadhesion. The protective effect of FEX-pure, FEX-market, and FEX-CS-SLNs against acetic acid-induced ulcerative colitis in rats was examined. Oral administration of FEX-CS-SLNs for 14 days before ulcerative colitis induction reversed UC symptoms and almost restored the intestinal mucosa to normal integrity and inhibited Phosphatidylinositol-3 kinase (73.6 %), protein kinase B (73.28 %), and elevated nuclear factor erythroid 2-related factor 2 (185.9 %) in colonic tissue. Additionally, FEX-CS-SLNs inhibited tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) to (70.79 % & 72.99 %) in colonic tissue. The ameliorative potential of FEX-CS-SLNs outperformed that of FEX-pure and FEX-market. The exceptional protective effect of FEX-CS-SLNs makes it a potentially effective oral system for managing ulcerative colitis.


Assuntos
Quitosana , Colite Ulcerativa , Lipossomos , Nanopartículas , Terfenadina/análogos & derivados , Ratos , Animais , Colite Ulcerativa/tratamento farmacológico , Portadores de Fármacos/efeitos adversos , Tamanho da Partícula
15.
Naunyn Schmiedebergs Arch Pharmacol ; 397(4): 1957-1969, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-37801146

RESUMO

Pheochromocytoma (PCC) is a neuroendocrine tumor that produces and secretes catecholamine from either the adrenal medulla or extra-adrenal locations. MicroRNAs (miRNAs, miR) can be used as biomarkers to detect cancer or the return of a previously treated disease. Blood-borne miRNAs might be envisioned as noninvasive markers of malignancy or prognosis, and new studies demonstrate that microRNAs are released in body fluids as well as tissues. MiRNAs have the potential to be therapeutic targets, which would greatly increase the restricted therapy options for adrenal tumors. This article aims to consolidate and synthesize the most recent studies on miRNAs in PCC, discussing their potential clinical utility as diagnostic and prognostic biomarkers while also addressing their limitations.


Assuntos
Neoplasias das Glândulas Suprarrenais , MicroRNAs , Feocromocitoma , Humanos , Feocromocitoma/diagnóstico , Feocromocitoma/genética , Feocromocitoma/patologia , Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/genética , Neoplasias das Glândulas Suprarrenais/patologia , Prognóstico , Biomarcadores Tumorais , Regulação Neoplásica da Expressão Gênica
16.
Pathol Res Pract ; 253: 155023, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38081104

RESUMO

Parkinson's disease (PD) is a debilitating neurological disorder characterized by the impairment of the motor system, resulting in symptoms such as resting tremor, cogwheel rigidity, bradykinesia, difficulty with gait, and postural instability. The occurrence of striatal dopamine insufficiency can be attributed to a notable decline in dopaminergic neurons inside the substantia nigra pars compacta. Additionally, the development of Lewy bodies serves as a pathological hallmark of PD. While current therapy approaches for PD aim to preserve dopaminergic neurons or replenish dopamine levels in the brain, it is important to acknowledge that achieving complete remission of the condition remains elusive. MicroRNAs (miRNAs, miR) are a class of small, non-coding ribonucleic acids involved in regulating gene expression at the post-transcriptional level. The miRNAs play a crucial part in the underlying pathogenic mechanisms of several neurodegenerative illnesses, including PD. The aim of this review is to explore the role of miRNAs in regulating genes associated with the onset and progression of PD, investigate the potential of miRNAs as a diagnostic tool, assess the effectiveness of targeting specific miRNAs as an alternative therapeutic strategy to impede disease advancement, and discuss the utilization of newly developed nanoparticles for delivering miRNAs as neurodegenerative therapies.


Assuntos
MicroRNAs , Doença de Parkinson , Humanos , MicroRNAs/metabolismo , Doença de Parkinson/diagnóstico , Doença de Parkinson/genética , Doença de Parkinson/terapia , Dopamina/uso terapêutico , Encéfalo/patologia
17.
Pathol Res Pract ; 253: 155007, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38061270

RESUMO

Alzheimer's disease (AD) is a multifaceted, advancing neurodegenerative illness that is responsible for most cases of neurological impairment and dementia in the aged population. As the disease progresses, affected individuals may experience cognitive decline, linguistic problems, affective instability, and behavioral changes. The intricate nature of AD reflects the altered molecular mechanisms participating in the affected human brain. MicroRNAs (miRNAs, miR) are essential for the intricate control of gene expression in neurobiology. miRNAs exert their influence by modulating the transcriptome of brain cells, which typically exhibit substantial genetic activity, encompassing gene transcription and mRNA production. Presently, comprehensive studies are being conducted on AD to identify miRNA-based signatures that are indicative of the disease pathophysiology. These findings can contribute to the advancement of our understanding of the mechanisms underlying this disorder and can inform the development of therapeutic interventions based on miRNA and related RNA molecules. Therefore, this comprehensive review provides a detailed holistic analysis of the latest advances discussing the emerging role of miRNAs in the progression of AD and their possible application as potential biomarkers and targets for therapeutic interventions in future studies.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , MicroRNAs , Humanos , Idoso , MicroRNAs/genética , MicroRNAs/metabolismo , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/genética , Doença de Alzheimer/terapia , Encéfalo/metabolismo , RNA Mensageiro , Biomarcadores/metabolismo
18.
Pathol Res Pract ; 254: 155147, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38246033

RESUMO

Asthma is a diverse inflammatory illness affecting the respiratory passages, leading to breathing challenges, bouts of coughing and wheezing, and, in severe instances, significant deterioration in quality of life. Epigenetic regulation, which involves the control of gene expression through processes such as post-transcriptional modulation of microRNAs (miRNAs), plays a role in the evolution of various asthma subtypes. In immune-mediated diseases, miRNAs play a regulatory role in the behavior of cells that form the airway structure and those responsible for defense mechanisms in the bronchi and lungs. They control various cellular processes such as survival, growth, proliferation, and the production of chemokines and immune mediators. miRNAs possess chemical and biological characteristics that qualify them as suitable biomarkers for diseases. They allow for the categorization of patients to optimize drug selection, thus streamlining clinical management and decreasing both the economic burden and the necessity for critical care related to the disease. This study provides a concise overview of the functions of miRNAs in asthma and elucidates their regulatory effects on the underlying processes of the disease. We provide a detailed account of the present status of miRNAs as biomarkers for categorizing asthma, identifying specific asthma subtypes, and selecting appropriate treatment options.


Assuntos
Asma , MicroRNAs , Humanos , MicroRNAs/genética , MicroRNAs/uso terapêutico , Epigênese Genética , Qualidade de Vida , Asma/diagnóstico , Asma/genética , Asma/tratamento farmacológico , Biomarcadores
19.
Pathol Res Pract ; 253: 155085, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38183822

RESUMO

Stroke, a major global cause of mortality, leads to a range of problems for those who survive. Besides its brutal events, stroke also tends to have a characteristic of recurrence, making it a complex disease involving intricate regulatory networks. One of the major cellular regulators is the non-coding RNAs (ncRNA), specifically microRNAs (miRNAs), thus the possible functions of miRNAs in the pathogenesis of stroke are discussed as well as the possibility of using miRNA-based therapeutic approaches. Firstly, the molecular mechanisms by which miRNAs regulate vital physiological processes, including synaptic plasticity, oxidative stress, apoptosis, and the integrity of the blood-brain barrier (BBB) are reviewed. The miRNA indirectly impacts stroke outcomes by regulating BBB function and angiogenesis through the targeting of transcription factors and angiogenic factors. In addition, the tendency for some miRNAs to be upregulated in response to hypoxia, which is a prevalent phenomenon in stroke and various neurological disorders, highlights the possibility that it controls hypoxia-inducible factor (HIF) signaling and angiogenesis, thereby influencing the integrity of the BBB as examples of the discussed mechanisms. Furthermore, this review explores the potential therapeutic targets that miRNAs may offer for stroke recovery and highlights their promising capacity to alleviate post-stroke complications. This review provides researchers and clinicians with valuable resources since it attempts to decipher the complex network of miRNA-mediated mechanisms in stroke. Additionally, the review addresses the interplay between miRNAs and stroke risk factors as well as clinical applications of miRNAs as diagnostic and prognostic markers.


Assuntos
MicroRNAs , Acidente Vascular Cerebral , Humanos , MicroRNAs/genética , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/genética , Fatores de Transcrição , Hipóxia , Apoptose
20.
Pathol Res Pract ; 254: 155102, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38211386

RESUMO

microRNAs (miRNAs) play a crucial role in brain growth and function. Hence, research on miRNA has the potential to reveal much about the etiology of neuropsychiatric diseases. Among these, schizophrenia (SZ) is a highly intricate and destructive neuropsychiatric ailment that has been thoroughly researched in the field of miRNA. Despite being a relatively recent area of study about miRNAs and SZ, this discipline has advanced enough to justify numerous reviews that summarize the findings from the past to the present. However, most reviews cannot cover all research, thus it is necessary to synthesize the large range of publications on this topic systematically and understandably. Consequently, this review aimed to provide evidence that miRNAs play a role in the pathophysiology and progression of SZ. They have also been investigated for their potential use as biomarkers and therapeutic targets.


Assuntos
MicroRNAs , Esquizofrenia , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Esquizofrenia/genética , Esquizofrenia/metabolismo , Biomarcadores , Encéfalo/metabolismo , Transdução de Sinais
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