Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 29
Filtrar
Más filtros













Base de datos
Intervalo de año de publicación
1.
Eur J Pharm Biopharm ; 196: 114205, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38311187

RESUMEN

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.


Asunto(s)
Quitosano , Colitis Ulcerosa , Liposomas , Nanopartículas , Terfenadina/análogos & derivados , Ratas , Animales , Colitis Ulcerosa/tratamiento farmacológico , Portadores de Fármacos/efectos adversos , Tamaño de la Partícula
2.
Pathol Res Pract ; 254: 155102, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38211386

RESUMEN

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.


Asunto(s)
MicroARNs , Esquizofrenia , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Esquizofrenia/genética , Esquizofrenia/metabolismo , Biomarcadores , Encéfalo/metabolismo , Transducción de Señal
3.
Pathol Res Pract ; 253: 155007, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38061270

RESUMEN

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.


Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , MicroARNs , Humanos , Anciano , MicroARNs/genética , MicroARNs/metabolismo , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/terapia , Encéfalo/metabolismo , ARN Mensajero , Biomarcadores/metabolismo
4.
Eur J Pharmacol ; 955: 175908, 2023 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-37451422

RESUMEN

Drug-induced acute kidney injury (AKI) represents a potentially serious disorder associated with increased morbidity and mortality. The presented study investigated the ability of the oral antidiabetic agent, dapagliflozin (DAPA), to preserve the kidneys of rats subjected to vancomycin (VCM)-induced AKI. Rats were injected with VCM (400 mg/kg; i.p daily) for 7 successive days to induce AKI. Rats that received VCM were pretreated with DAPA at 5 or 10 mg/kg; p.o daily for 14 successive days. Vancomycin-treated rats depicted renal tubular damage, decline in renal function, and renal morphological alterations. Impairment of renal antioxidant machinery and propagation of renal cell apoptosis was apparent in the setting of VCM overdose. Pretreatment of VCM rats with DAPA, particularly at 10 mg/kg, effectively attenuated NADPH oxidase-4 (NOX4)-induced renal ROS, hampered activin A activation, and repressed miRNA-21/PTEN/pAKT signaling. These events were associated with impeding the expression of renal p-FOXO3a/t-FOXO3a ratio and promoting the nuclear localization of FOXO3a immnoexpression, enhancing renal antioxidant enzymes. At the same time, DAPA pretreatment improved renal function indices and alleviated the kidney injury markers, NGAL, and KIM-1, accompanied by restoring the normal renal histopathological structure. Regarding renal apoptosis, DAPA suppressed the expression of Bax/Bcl2 ratio and caspase-3. This study demonstrates that DAPA ameliorates VCM-induced AKI in rats via modulating renal oxidative stress, presumably by interfering with NOX4/activin A/miRNA-21 cascade and augmenting t-FOXO3a expression as well as dampening renal cell apoptosis.

5.
Pathol Res Pract ; 248: 154611, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37315401

RESUMEN

Testicular germ cell tumors (TGCTs) are the most common testicular neoplasms in adolescents and young males. Understanding the genetic basis of TGCTs represents a growing need to cope with the increased incidence of these neoplasms. Although the cure rates have been comparatively increased, investigation of mechanisms underlying the incidence, progression, metastasis, recurrence, and therapy resistance is still necessary. Early diagnosis and non-compulsory clinical therapeutic agents without long-term side effects are now required to reduce the cancer burden, especially in the younger age groups. MicroRNAs (miRNAs) control an extensive range of cellular functions and exhibit a pivotal action in the development and spreading of TGCTs. Because of their dysregulation and disruption in function, miRNAs have been linked to the malignant pathophysiology of TGCTs by influencing many cellular functions involved in the disease. These biological processes include increased invasive and proliferative perspective, cell cycle dysregulation, apoptosis disruption, stimulation of angiogenesis, epithelial-mesenchymal transition (EMT) and metastasis, and resistance to certain treatments. Herein, we present an up-to-date review of the biogenesis of miRNAs, miRNA regulatory mechanisms, clinical challenges, and therapeutic interventions of TGCTs, and role of nanoparticles in the treatment of TGCTs.


Asunto(s)
MicroARNs , Neoplasias de Células Germinales y Embrionarias , Neoplasias Testiculares , Masculino , Adolescente , Humanos , MicroARNs/genética , MicroARNs/uso terapéutico , Neoplasias de Células Germinales y Embrionarias/genética , Neoplasias Testiculares/genética , Neoplasias Testiculares/patología , Transducción de Señal/genética
6.
Pathol Res Pract ; 248: 154612, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37327566

RESUMEN

Testicular cancer (TC) is one of the most frequently incident solid tumors in males. A growing prevalence has been documented in developed countries. Although recent advances have made TC an exceedingly treatable cancer, numerous zones in TC care still have divisive treatment decisions. In addition to physical examination and imaging techniques, conventional serum tumor markers have been traditionally used for the diagnosis of testicular germ cell tumors (TGCT). Unlike other genital and urinary tract tumors, recent research methods have not been broadly used in TGCTs. Even though several challenges in TC care must be addressed, a dedicated group of biomarkers could be particularly beneficial to help classify patient risk, detect relapse early, guide surgery decisions, and tailor follow-up. Existing tumor markers (Alpha-fetoprotein, human chorionic gonadotrophin, and lactate dehydrogenase) have limited accuracy and sensitivity when used as diagnostic, prognostic, or predictive markers. At present, microRNAs (miRNA or miR) play a crucial role in the process of several malignancies. The miRNAs exhibit pronounced potential as novel biomarkers since they reveal high stability in body fluids, are easily detected, and are relatively inexpensive in quantitative assays. In this review, we aimed to shed light on the recent novelties in developing microRNAs as diagnostic and prognostic markers in TC and discuss their clinical applications in TC management.


Asunto(s)
MicroARNs , Neoplasias de Células Germinales y Embrionarias , Neoplasias Testiculares , Masculino , Humanos , MicroARNs/genética , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/genética , Neoplasias Testiculares/patología , Neoplasias de Células Germinales y Embrionarias/diagnóstico , Neoplasias de Células Germinales y Embrionarias/genética , Biomarcadores de Tumor/genética , Resistencia a Medicamentos
7.
Pathol Res Pract ; 246: 154512, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37172525

RESUMEN

Long non-coding RNAs (lncRNAs) are a class of noncoding RNAs with a length larger than 200 nucleotides that participate in various diseases and biological processes as they can control gene expression by different mechanisms. Rheumatoid arthritis (RA) is an inflammatory autoimmune disorder characterized by symmetrical destructive destruction of distal joints as well as extra-articular involvement. Different studies have documented and proven the abnormal expression of lncRNAs in RA patients. Various lncRNAs have proven potential as biomarkers and targets for diagnosing, prognosis and treating RA. This review will focus on RA pathogenesis, clinical implications, and related lncRNA expressions that help to identify new biomarkers and treatment targets.


Asunto(s)
Artritis Reumatoide , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/genética , Artritis Reumatoide/genética , Artritis Reumatoide/metabolismo , Artritis Reumatoide/patología , ARN no Traducido , Biomarcadores/metabolismo
8.
Pathol Res Pract ; 245: 154440, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37031531

RESUMEN

MicroRNAs (miRNAs), short, highly conserved non-coding RNA, influence gene expression by sequential mechanisms such as mRNA breakdown or translational repression. Many biological processes depend on these regulating substances, thus changes in their expression have an impact on the maintenance of cellular homeostasis and result in the emergence of a variety of diseases. Relevant studies have shown in recent years that miRNAs are involved in many stages of bone development and growth. Additionally, abnormal production of miRNA in bone tissues has been closely associated with the development of numerous bone disorders, such as osteonecrosis, bone cancer, and bone metastases. Many pathological processes, including bone loss, metastasis, the proliferation of osteosarcoma cells, and differentiation of osteoblasts and osteoclasts, are under the control of miRNAs. By bringing together the most up-to-date information on the clinical relevance of miRNAs in such diseases, this study hopes to further the study of the biological features of miRNAs in bone disorders and explore their potential as a therapeutic target.


Asunto(s)
Neoplasias Óseas , MicroARNs , Humanos , MicroARNs/metabolismo , Huesos/metabolismo , Osteoclastos , Osteoblastos/metabolismo , Neoplasias Óseas/genética
9.
Pathol Res Pract ; 245: 154437, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37030167

RESUMEN

Cholangiocarcinoma (CCA), the second most frequent liver cancer after hepatocellular carcinoma, has been rising worldwide in recent epidemiological research. This neoplasia's pathogenesis is poorly understood. Yet, recent advances have illuminated the molecular processes of cholangiocyte malignancy and growth. Late diagnosis, ineffective therapy, and resistance to standard treatments contribute to this malignancy's poor prognosis. So, to develop efficient preventative and therapy methods, the molecular pathways that cause this cancer must be better understood. MicroRNAs (miRNAs) are non-coding ribonucleic acids (ncRNAs) that influence gene expression. Biliary carcinogenesis involves abnormally expressed miRNAs that act as oncogenes or tumor suppressors (TSs). The miRNAs regulate multiple gene networks and are involved in cancer hallmarks like reprogramming of cellular metabolism, sustained proliferative signaling, evasion of growth suppressors, replicative immortality, induction/access to the vasculature, activation of invasion and metastasis, and avoidance of immune destruction. In addition, numerous ongoing clinical trials are demonstrating the efficacy of therapeutic strategies based on miRNAs as powerful anticancer agents. Here, we will update the research on CCA-related miRNAs and explain their regulation involved in the molecular pathophysiology of this malignancy. Eventually, we will disclose their potential as clinical biomarkers and therapeutic tools in CCA.


Asunto(s)
Neoplasias de los Conductos Biliares , Colangiocarcinoma , Neoplasias Hepáticas , MicroARNs , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Virulencia , Colangiocarcinoma/genética , Colangiocarcinoma/terapia , Colangiocarcinoma/patología , Transducción de Señal/genética , Neoplasias Hepáticas/patología , Neoplasias de los Conductos Biliares/genética , Neoplasias de los Conductos Biliares/terapia , Neoplasias de los Conductos Biliares/patología , Conductos Biliares Intrahepáticos/patología , Regulación Neoplásica de la Expresión Génica/genética
10.
Pathol Res Pract ; 245: 154439, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37028108

RESUMEN

Renal cell carcinoma (RCC) has the highest mortality rate of all genitourinary cancers, and its prevalence has grown over time. While RCC can be surgically treated and recurrence is only probable in a tiny proportion of patients, early diagnosis is crucial. Mutations in a large number of oncogenes and tumor suppressor genes contribute to pathway dysregulation in RCC. MicroRNAs (miRNAs) have considerable promise as biomarkers for detecting cancer due to their special combination of properties. Several miRNAs have been proposed as a diagnostic or monitoring tool for RCC based on their presence in the blood or urine. Moreover, the expression profile of particular miRNAs has been associated with the response to chemotherapy, immunotherapy, or targeted therapeutic options like sunitinib. The goal of this review is to go over the development, spread, and evolution of RCC. Also, we emphasize the outcomes of studies that examined the use of miRNAs in RCC patients as biomarkers, therapeutic targets, or modulators of responsiveness to treatment modalities.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , MicroARNs , Humanos , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/terapia , Carcinoma de Células Renales/metabolismo , MicroARNs/metabolismo , Neoplasias Renales/genética , Neoplasias Renales/terapia , Neoplasias Renales/metabolismo , Biomarcadores de Tumor/metabolismo , Oncogenes , Regulación Neoplásica de la Expresión Génica
11.
Arch Pharm Res ; 46(4): 323-338, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36959348

RESUMEN

Alcoholic liver disease (ALD) refers to hepatic ailments induced by excessive alcohol intake. The pathogenesis of ALD comprises a complex interplay between various mechanistic pathways, among which inflammation and oxidative stress are key players. Boswellic acids (BAs), found in Boswellia serrata, have shown hepatoprotective effects owing to their antioxidant and anti-inflammatory activities, nevertheless, their therapeutic potential against ALD has not been previously investigated. Hence, this study was performed to depict the possible protective effect of BAs and detect their underlying mechanism of action in an experimentally-induced ALD mouse model. Male BALB/c mice were equally categorized into six groups: control, BAs-treated, ALD, and ALD that received BAs at three-dose levels (125, 250, and 500 mg/kg) by oral gavage for 14 days. Results showed that the high dose of BAs had the most protective impact against ALD according to histopathology examination, blood alcohol concentration (BAC), and liver function enzymes. Mechanistic investigations revealed that BAs (500 mg/kg) caused a significant decrease in cytochrome P450 2E1(CYP2E1), nicotine adenine dinucleotide phosphate oxidase (NOX) 1/2/4, p38 mitogen-activated protein kinase (MAPK), and sterol regulatory element-binding protein-1c (SREBP-1c) levels, and the expression of miR-155, yet increased peroxisome proliferator-activated receptor alpha (PPARα) levels. This led to an improvement in lipid profile and reduced hepatic inflammation, oxidative stress, and apoptosis indices. In summary, our study concludes that BAs can protect against ethanol-induced hepatic injury, via modulating NOX/p38 MAPK/PPARα pathways and miR-155 expression.


Asunto(s)
Hepatopatías Alcohólicas , MicroARNs , Animales , Masculino , Ratones , Nivel de Alcohol en Sangre , Inflamación/metabolismo , Hígado , Hepatopatías Alcohólicas/tratamiento farmacológico , Hepatopatías Alcohólicas/prevención & control , Hepatopatías Alcohólicas/etiología , MicroARNs/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , PPAR alfa/metabolismo , PPAR alfa/farmacología , PPAR alfa/uso terapéutico , Transducción de Señal
12.
Pathol Res Pract ; 243: 154375, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36801506

RESUMEN

MicroRNAs (miRNAs) are a class of short, non-coding RNAs that function post-transcriptionally to regulate gene expression by binding to particular mRNA targets and causing destruction of the mRNA or translational inhibition of the mRNA. The miRNAs control the range of liver activities, from the healthy to the unhealthy. Considering that miRNA dysregulation is linked to liver damage, fibrosis, and tumorigenesis, miRNAs are a promising therapeutic strategy for the evaluation and treatment of liver illnesses. Recent findings on the regulation and function of miRNAs in liver diseases are discussed, with an emphasis on miRNAs that are highly expressed or enriched in hepatocytes. Alcohol-related liver illness, acute liver toxicity, viral hepatitis, hepatocellular carcinoma, liver fibrosis, liver cirrhosis, and exosomes in chronic liver disease all emphasize the roles and target genes of these miRNAs. We briefly discuss the function of miRNAs in the etiology of liver diseases, namely in the transfer of information between hepatocytes and other cell types via extracellular vesicles. Here we offer some background on the use of miRNAs as biomarkers for the early prognosis, diagnosis, and assessment of liver diseases. The identification of biomarkers and therapeutic targets for liver disorders will be made possible by future research into miRNAs in the liver, which will also help us better understand the pathogeneses of liver diseases.


Asunto(s)
Carcinoma Hepatocelular , Hepatopatías , Neoplasias Hepáticas , MicroARNs , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/metabolismo , Carcinoma Hepatocelular/patología , Biomarcadores , Cirrosis Hepática , ARN Mensajero/genética , Hepatopatías/genética , Hepatopatías/terapia
13.
Curr Issues Mol Biol ; 45(1): 721-737, 2023 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-36661534

RESUMEN

Epigenetic modifications play a pivotal role in autoimmune/inflammatory disorders and could establish a bridge between personalized medicine and disease epidemiological contexts. We sought to investigate the role of epigenetic modifications beside genetic alterations in the MEFV gene in familial Mediterranean fever (FMF). The study comprised 63 FMF patients diagnosed according to the Tel Hashomer criteria: 37 (58.7%) colchicine-responders, 26 (41.3%) non-responders, and 19 matched healthy controls. MEFV mutations were detected using a CE/IVD-labeled 4-230 FMF strip assay. DNA methylation of MEFV gene exon 2 was measured using bisulfite modification and related to pyrin level, phenotypic picture, MEFV mutations, disease severity, serum amyloid A (SAA), CRP, ESR, disease severity, and colchicine response. Our results showed that FMF patients exhibited significantly higher methylation percentage (p < 0.001) and lower pyrin levels (p < 0.001) compared to the control. The MEFV gene M694I mutation was the most commonly reported mutation (p < 0.004). High methylation percentage of the MEFV exon 2 and low pyrin concentration were correlated with disease severity, high SAA, ESR levels, H-pylori, and renal calculi. In conclusion, this study highlights the relation between high methylation percentage, reduced pyrin level, and different biomarkers in FMF, which underscores their role in the pathogenesis of FMF and could be considered as potential therapeutic targets.

14.
Int J Biol Macromol ; 224: 1541-1565, 2023 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-36328268

RESUMEN

Breast cancer (BC) is the most common cancer in women and poses a serious threat to their health. Despite familiarity with factors affecting its etiology, initiation, progression, treatment strategies, and even resistance to therapy, it is considered a significant problem for women. However, several factors have greatly affected previous aspects affecting BC progression and treatment in the last decades. miRNAs are short non-coding RNA sequences that regulate gene expression by inhibiting the translation of the target mRNA. miRNAs play a crucial role in BC pathogenesis by promoting cancer stem cell (CSCs) proliferation, postponing apoptosis, continuing the cell cycle, and endorsing invasion, angiogenesis, and metastasis. Similarly, miRNAs influence important BC-related molecular pathways such as the PI3K/AKT/mTOR signaling pathway, the Wnt/ß-catenin system, JAK/STAT signaling pathway, and the MAPK signaling pathway. Moreover, miRNAs affect the treatment response of BC to chemo and radiotherapy. Consequently, this review aims to provide an acquainted summary of oncomiRs and tumor suppressor (TS) miRNAs and their potential role in BC pathogenesis and therapy responses by focusing on the molecular pathways that drive them.


Asunto(s)
Neoplasias de la Mama , MicroARNs , Humanos , Femenino , MicroARNs/genética , Neoplasias de la Mama/patología , Fosfatidilinositol 3-Quinasas/metabolismo , Transducción de Señal/genética , Genes Supresores de Tumor , Regulación Neoplásica de la Expresión Génica
15.
Pharmaceuticals (Basel) ; 15(10)2022 Oct 13.
Artículo en Inglés | MEDLINE | ID: mdl-36297374

RESUMEN

In the current work, we designed and synthesized three families of non-fused and fused compounds based on cyanopyridone: derivatives of 6-amino-1,2-dihydropyridine-3,5-dicarbonitrile (5a-f) and 3,4,7,8-tetrahydro pyrimidine-6-carbonitrile (6a-b and 7a-e). The newly synthesized compounds' structure were determined using a variety of techniques, including 1H NMR, 13C NMR, mass spectrum, infrared spectroscopy, and elemental analysis. The developed compounds were tested for the ability to inhibit the growth of breast adenocarcinoma (MCF-7) and hepatic adenocarcinoma (HepG2) cell lines using MTT assay. Some of the synthesized compounds were more effective towards the cancer cell lines than the standard treatment taxol. The best antiproliferative activities were demonstrated by non-fused cyanopyridones 5a and 5e against the MCF-7 cell line (IC50 = 1.77 and 1.39 µM, respectively) and by compounds 6b and 5a against the HepG2 cell line (IC50 = 2.68 and 2.71 µM, respectively). We further explored 5a and 5e, the two most potent compounds against the MCF-7 cell line, for their ability to inhibit VEGFR-2 and HER-2. Finally, docking and molecular dynamics simulations were performed as part of the molecular modeling investigation to elucidate the molecular binding modes of the tested compounds, allowing for a more thorough comprehension of the activity of compounds 5a and 5e.

16.
Polymers (Basel) ; 14(16)2022 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-36015608

RESUMEN

Traditional cancer treatments include surgery, radiation, and chemotherapy. According to medical sources, chemotherapy is still the primary method for curing or treating cancer today and has been a major contributor to the recent decline in cancer mortality. Nanocomposites based on polymers and metal nanoparticles have recently received the attention of researchers. In the current study, a nanocomposite was fabricated based on carboxymethyl cellulose and silver nanoparticles (CMC-AgNPs) and their antibacterial, antifungal, and anticancer activities were evaluated. The antibacterial results revealed that CMC-AgNPs have promising antibacterial activity against Gram-negative (Klebsiella oxytoca and Escherichia coli) and Gram-positive bacteria (Bacillus cereus and Staphylococcus aureus). Moreover, CMC-AgNPs exhibited antifungal activity against filamentous fungi such as Aspergillus fumigatus, A. niger, and A. terreus. Concerning the HepG2 hepatocellular cancer cell line, the lowest IC50 values (7.9 ± 0.41 µg/mL) were recorded for CMC-AgNPs, suggesting a strong cytotoxic effect on liver cancer cells. As a result, our findings suggest that the antitumor effect of these CMC-Ag nanoparticles is due to the induction of apoptosis and necrosis in hepatic cancer cells via increased caspase-8 and -9 activities and diminished levels of VEGFR-2. In conclusion, CMC-AgNPs exhibited antibacterial, antifungal, and anticancer activities, which can be used in the pharmaceutical and medical fields.

17.
Int J Biol Macromol ; 214: 583-600, 2022 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-35768045

RESUMEN

Colorectal cancer (CRC) is the world's third most prevalent cancer and the main cause of cancer-related mortality. A lot of work has been put into improving CRC patients' clinical care, including the development of more effective methods and wide biomarkers variety for prognostic, and diagnostic purposes. MicroRNAs (miRNAs) regulate a variety of cellular processes and play a significant role in the CRC progression and spread via controlling their target gene expression by translation inhibition or mRNA degradation. Consequently, dysregulation and disruption in their function, miRNAs are linked to CRC malignant pathogenesis by controlling several cellular processes involved in the CRC. These cellular processes include increased proliferative and invasive capacity, cell cycle aberration, evasion of apoptosis, enhanced EMT, promotion of angiogenesis and metastasis, and decreased sensitivity to major treatments. The miRNAs control cellular processes in CRC via regulation of pathways such as Wnt/ß-catenin signaling, PTEN/AKT/mTOR axis, KRAS, TGFb signaling, VEGFR, EGFR, and P53. Hence, the goal of this review was to review miRNA biogenesis and present an updated summary of oncogenic and tumor suppressor (TS) miRNAs and their potential implication in CRC pathogenesis and responses to chemotherapy and radiotherapy. We also summarise the biological importance and clinical applications of miRNAs in the CRC.


Asunto(s)
Neoplasias Colorrectales , MicroARNs , Carcinogénesis/genética , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/terapia , Regulación Neoplásica de la Expresión Génica , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Vía de Señalización Wnt
18.
Pathol Res Pract ; 233: 153886, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35405621

RESUMEN

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related deaths worldwide. HCC initiation, progression, and therapy failure are all influenced by various variables, including microRNAs (miRNAs). miRNAs are short non-coding RNA sequences that modulate target mRNA expression by deteriorating or repressing translation. miRNAs play an imperative role in HCC pathogenesis by triggering the induction of cancer stem cells (CSCs) and their proliferation, while also delaying apoptosis, sustaining the cell cycle, and inspiring angiogenesis, invasion, and metastasis. Additionally, miRNAs modulate crucial HCC-related molecular pathways such as the p53 pathway, the Wnt/ß-catenin pathway, VEGFR2, and PTEN/PI3K/AKT pathway. Consequently, the goal of this review was to give an up-to-date overview of oncogenic and tumor suppressor (TS) miRNAs, as well as their potential significance in HCC pathogenesis and treatment responses, highlighting their underpinning molecular pathways in HCC initiation and progression. Similarly, the biological importance and clinical application of miRNAs in HCC are summarized.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroARNs , Carcinogénesis/genética , Carcinoma Hepatocelular/patología , Humanos , Neoplasias Hepáticas/patología , MicroARNs/genética , Transducción de Señal
19.
Int J Biol Macromol ; 197: 141-156, 2022 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-34968539

RESUMEN

Prostate cancer (PC) is the third-leading cause of cancer-related deaths worldwide. Although the current treatment strategies are progressing rapidly, PC is still representing a substantial medical problem for affected patients. Several factors are involved in PC initiation, progression, and treatments failure including microRNAs (miRNAs). The miRNAs are endogenous short non-coding RNA sequence negatively regulating target mRNA expression via degradation or translation repression. miRNAs play a pivotal role in PC pathogenesis through its ability to initiate the induction of cancer stem cells (CSCs) and proliferation, as well as sustained cell cycle, evading apoptosis, invasion, angiogenesis, and metastasis. Furthermore, miRNAs regulate major molecular pathways affecting PC such as the androgen receptor (AR) pathway, p53 pathway, PTEN/PI3K/AKT pathway, and Wnt/ß-catenin pathway. Furthermore, miRNAs alter PC therapeutic response towards the androgen deprivation therapy (ADT), chemotherapy and radiation therapy (RT). Thus, the understanding and profiling of the altered miRNAs expression in PC could be utilized as a non-invasive biomarker for the early diagnosis as well as for patient sub-grouping with different prognoses for individualized treatment. Accordingly, in the current review, we summarized in updated form the roles of various oncogenic and tumor suppressor (TS) miRNAs in PC, revealing their underlying molecular mechanisms in PC initiation and progression.


Asunto(s)
MicroARNs
20.
Pharm Res ; 38(11): 1821-1838, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34853982

RESUMEN

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.


Asunto(s)
Bloqueadores del Receptor Tipo 1 de Angiotensina II/administración & dosificación , Antiinflamatorios no Esteroideos/efectos adversos , Imidazoles/administración & dosificación , Indometacina/efectos adversos , Úlcera Gástrica/tratamiento farmacológico , Tetrazoles/administración & dosificación , Bloqueadores del Receptor Tipo 1 de Angiotensina II/farmacocinética , Animales , Disponibilidad Biológica , Modelos Animales de Enfermedad , Liberación de Fármacos , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/patología , Hemo Oxigenasa (Desciclizante)/metabolismo , Humanos , Imidazoles/farmacocinética , Liposomas , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Masculino , Factor 2 Relacionado con NF-E2/metabolismo , Ratas , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/patología , Tetrazoles/farmacocinética
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA