Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 20
Filtrar
1.
J Electrocardiol ; 84: 112-122, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38631278

RESUMO

AIM: QTc interval prolongation is a growing global issue which can cause torsades de pointes, a potentially fatal arrhythmia. We aimed to identify risk factors for prolonged QT interval in men and women. METHODS: The Mashhad stroke and heart atherosclerotic disorder (MASHAD) cohort study collected electrocardiogram interval data. QT was corrected for heart rate using the Bazett's formula. Ordinal logistic regression with crude (univariable) and adjusted (multivariate) association analyses in the form of odds ratio and corresponding 95% confidence interval (CI) were used to identify the factors associated with QTc prolongation. RESULTS: A total of 8878 individuals including 5318 females and 3560 males, aged 35 to 65 years, were included in this cross-sectional study. Participants with QTc prolongation were more likely to be older and have hypercholesterolemia, hypertension (HTN), and Type 2 diabetes mellitus (T2DM), but to have lower levels of physical activity (P < 0.05). Age (OR = 1.68, 95%CI = 1.18-2.39), hypercholesterolemia (OR = 1.77, 95%CI = 1.24-2.51), HTN (OR = 1.36, 95%CI = 1.06-1.73), T2DM (OR = 1.59, 95%CI = 1.19-2.13), severe anxiety (OR = 1.80, 95%CI = 1.05-3.11) and mild depression (OR = 1.38, 95%CI = 1.01-1.88) were independent risk factors for prolonged QTc interval in men. For women, only HTN (OR = 1.29, 95%CI = 1.02-1.63) and T2DM (OR = 1.50, 95%CI = 1.14-1.97) were independent risk factors. CONCLUSIONS: Older age, Hypercholesterolemia, HTN, T2DM, severe anxiety and mild depression in men, and HTN and T2DM in women were associated with high risk of prolonged QTc interval. Healthcare practitioners should be aware of the risk factors of QTc interval prolongation and should exercise caution in the management of certain patients.


Assuntos
Eletrocardiografia , Síndrome do QT Longo , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Síndrome do QT Longo/epidemiologia , Adulto , Irã (Geográfico)/epidemiologia , Idoso , Fatores de Risco , Estudos Transversais , Estudos de Coortes , Comorbidade , Hipertensão/epidemiologia , Hipercolesterolemia/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia
2.
Virol J ; 21(1): 67, 2024 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-38509569

RESUMO

Since 1997, highly pathogenic avian influenza viruses, such as H5N1, have been recognized as a possible pandemic hazard to men and the poultry business. The rapid rate of mutation of H5N1 viruses makes the whole process of designing vaccines extremely challenging. Here, we used an in silico approach to design a multi-epitope vaccine against H5N1 influenza A virus using hemagglutinin (HA) and neuraminidase (NA) antigens. B-cell epitopes, Cytotoxic T lymphocyte (CTL) and Helper T lymphocyte (HTL) were predicted via IEDB, NetMHC-4 and NetMHCII-2.3 respectively. Two adjuvants consisting of Human ß-defensin-3 (HßD-3) along with pan HLA DR-binding epitope (PADRE) have been chosen to induce more immune response. Linkers including KK, AAY, HEYGAEALERAG, GPGPGPG and double EAAAK were utilized to link epitopes and adjuvants. This construct encodes a protein having 350 amino acids and 38.46 kDa molecular weight. Antigenicity of ~ 1, the allergenicity of non-allergen, toxicity of negative and solubility of appropriate were confirmed through Vaxigen, AllerTOP, ToxDL and DeepSoluE, respectively. The 3D structure of H5N1 was refined and validated with a Z-Score of - 0.87 and an overall Ramachandran of 99.7%. Docking analysis showed H5N1 could interact with TLR7 (docking score of - 374.08 and by 4 hydrogen bonds) and TLR8 (docking score of - 414.39 and by 3 hydrogen bonds). Molecular dynamics simulations results showed RMSD and RMSF of 0.25 nm and 0.2 for H5N1-TLR7 as well as RMSD and RMSF of 0.45 nm and 0.4 for H5N1-TLR8 complexes, respectively. Molecular Mechanics Poisson-Boltzmann Surface Area (MM/PBSA) confirmed stability and continuity of interaction between H5N1-TLR7 with the total binding energy of - 29.97 kJ/mol and H5N1-TLR8 with the total binding energy of - 23.9 kJ/mol. Investigating immune response simulation predicted evidence of the ability to stimulate T and B cells of the immunity system that shows the merits of this H5N1 vaccine proposed candidate for clinical trials.


Assuntos
Virus da Influenza A Subtipo H5N1 , Vacinas , Animais , Humanos , Virus da Influenza A Subtipo H5N1/genética , Epitopos de Linfócito T/genética , Receptor 7 Toll-Like , Receptor 8 Toll-Like , Epitopos de Linfócito B , Biologia Computacional/métodos , Simulação de Acoplamento Molecular , Vacinas de Subunidades Antigênicas/genética
3.
BMC Microbiol ; 24(1): 16, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38183010

RESUMO

Studying the effects of the microbiome on the development of different types of cancer has recently received increasing research attention. In this context, the microbial content of organs of the gastrointestinal tract has been proposed to play a potential role in the development of pancreatic cancer (PC). Proposed mechanisms for the pathogenesis of PC include persistent inflammation caused by microbiota leading to an impairment of antitumor immune surveillance and altered cellular processes in the tumor microenvironment. The limited available diagnostic markers that can currently be used for screening suggest the importance of microbial composition as a non-invasive biomarker that can be used in clinical settings. Samples including saliva, stool, and blood can be analyzed by 16 s rRNA sequencing to determine the relative abundance of specific bacteria. Studies have shown the potentially beneficial effects of prebiotics, probiotics, antibiotics, fecal microbial transplantation, and bacteriophage therapy in altering microbial diversity, and subsequently improving treatment outcomes. In this review, we summarize the potential impact of the microbiome in the pathogenesis of PC, and the role these microorganisms might play as biomarkers in the diagnosis and determining the prognosis of patients. We also discuss novel treatment methods being used to minimize or prevent the progression of dysbiosis by modulating the microbial composition. Emerging evidence is supportive of applying these findings to improve current therapeutic strategies employed in the treatment of PC.


Assuntos
Microbiota , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/terapia , Biomarcadores , Antibacterianos , Disbiose/terapia , Microambiente Tumoral
4.
Curr Drug Targets ; 24(17): 1335-1345, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38053355

RESUMO

Pancreatic cancer (PC) is one the most lethal malignancies worldwide affecting around half a million individuals each year. The treatment of PC is relatively difficult due to the difficulty in making an early diagnosis. Transforming growth factor-beta (TGF-ß) is a multifunctional factor acting as both a tumor promoter in early cancer stages and a tumor suppressor in advanced disease. Programmed death-ligand 1 (PD-L1) is a ligand of programmed death-1 (PD-1), an immune checkpoint receptor, allowing tumor cells to avoid elimination by immune cells. Recently, targeting the TGF-ß signaling and PD-L1 pathways has emerged as a strategy for cancer therapy. In this review, we have summarized the current knowledge regarding these pathways and their contribution to tumor development with a focus on PC. Moreover, we have reviewed the role of TGF-ß and PD-L1 blockade in the treatment of various cancer types, including PC, and discussed the clinical trials evaluating TGF-ß and PD-L1 antagonists in PC patients.


Assuntos
Antígeno B7-H1 , Neoplasias Pancreáticas , Humanos , Fator de Crescimento Transformador beta/metabolismo , Ligantes , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Fatores de Crescimento Transformadores , Microambiente Tumoral
5.
Sci Rep ; 13(1): 20489, 2023 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-37993474

RESUMO

Non-alcoholic fatty liver disease (NAFLD) comprises a range of chronic liver diseases that result from the accumulation of excess triglycerides in the liver, and which, in its early phases, is categorized NAFLD, or hepato-steatosis with pure fatty liver. The mortality rate of non-alcoholic steatohepatitis (NASH) is more than NAFLD; therefore, diagnosing the disease in its early stages may decrease liver damage and increase the survival rate. In the current study, we screened the gene expression data of NAFLD patients and control samples from the public dataset GEO to detect DEGs. Then, the correlation betweenbetween the top selected DEGs and clinical data was evaluated. In the present study, two GEO datasets (GSE48452, GSE126848) were downloaded. The dysregulated expressed genes (DEGs) were identified by machine learning methods (Penalize regression models). Then, the shared DEGs between the two training datasets were validated using validation datasets. ROC-curve analysis was used to identify diagnostic markers. R software analyzed the interactions between DEGs, clinical data, and fatty liver. Ten novel genes, including ABCF1, SART3, APC5, NONO, KAT7, ZPR1, RABGAP1, SLC7A8, SPAG9, and KAT6A were found to have a differential expression between NAFLD and healthy individuals. Based on validation results and ROC analysis, NR4A2 and IGFBP1b were identified as diagnostic markers. These key genes may be predictive markers for the development of fatty liver. It is recommended that these key genes are assessed further as possible predictive markers during the development of fatty liver.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/genética , Cirrose Hepática/diagnóstico , Biologia Computacional , Aprendizado de Máquina , Proteínas Adaptadoras de Transdução de Sinal , Antígenos de Neoplasias , Proteínas de Ligação a RNA , Transportadores de Cassetes de Ligação de ATP , Histona Acetiltransferases
6.
Curr Pharm Des ; 29(31): 2450-2460, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37877510

RESUMO

We have reviewed the potential use of bioactive peptides in the treatment of gastrointestinal (GI) malignancies, which are a significant cause of morbidity and mortality globally. Conventional therapies, such as surgery, chemotherapy, and radiotherapy, are associated with numerous side effects that may lead to longterm complications. Bioactive peptides are short-chain amino acids that can be extracted from natural sources or synthesized, and they have various potential health benefits, including anti-inflammatory, anti-hypertensive, antioxidant, antimicrobial, and anti-cancer properties. Bioactive peptides can be acquired from animal or plant sources, and can be classified based on their function, such as ACE-inhibiting, antimicrobial, and electrolyte- regulating peptides. Recent studies have demonstrated the promising role of bioactive peptides in tumor suppression, especially when combined with conventional therapies. In this study, we have reviewed the beneficial properties of bioactive peptides and their role in suppressing tumor activity. The mechanisms of bioactive peptides in tumor suppression are discussed. We have further reviewed the findings of preclinical and clinical studies that have investigated the application of bioactive peptides in the treatment of GI cancers. This review highlights the potential use of bioactive peptides as a promising treatment method for GI malignancies to increase the quality of life of GI cancer patients.


Assuntos
Anti-Infecciosos , Neoplasias Gastrointestinais , Animais , Humanos , Qualidade de Vida , Peptídeos/farmacologia , Peptídeos/uso terapêutico , Peptídeos/química , Neoplasias Gastrointestinais/tratamento farmacológico , Antioxidantes/química
7.
Sci Rep ; 13(1): 16678, 2023 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-37794108

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is associated with a very poor prognosis. Therefore, there has been a focus on identifying new biomarkers for its early diagnosis and the prediction of patient survival. Genome-wide RNA and microRNA sequencing, bioinformatics and Machine Learning approaches to identify differentially expressed genes (DEGs), followed by validation in an additional cohort of PDAC patients has been undertaken. To identify DEGs, genome RNA sequencing and clinical data from pancreatic cancer patients were extracted from The Cancer Genome Atlas Database (TCGA). We used Kaplan-Meier analysis of survival curves was used to assess prognostic biomarkers. Ensemble learning, Random Forest (RF), Max Voting, Adaboost, Gradient boosting machines (GBM), and Extreme Gradient Boosting (XGB) techniques were used, and Gradient boosting machines (GBM) were selected with 100% accuracy for analysis. Moreover, protein-protein interaction (PPI), molecular pathways, concomitant expression of DEGs, and correlations between DEGs and clinical data were analyzed. We have evaluated candidate genes, miRNAs, and a combination of these obtained from machine learning algorithms and survival analysis. The results of Machine learning identified 23 genes with negative regulation, five genes with positive regulation, seven microRNAs with negative regulation, and 20 microRNAs with positive regulation in PDAC. Key genes BMF, FRMD4A, ADAP2, PPP1R17, and CACNG3 had the highest coefficient in the advanced stages of the disease. In addition, the survival analysis showed decreased expression of hsa.miR.642a, hsa.mir.363, CD22, BTNL9, and CTSW and overexpression of hsa.miR.153.1, hsa.miR.539, hsa.miR.412 reduced survival rate. CTSW was identified as a novel genetic marker and this was validated using RT-PCR. Machine learning algorithms may be used to Identify key dysregulated genes/miRNAs involved in the disease pathogenesis can be used to detect patients in earlier stages. Our data also demonstrated the prognostic and diagnostic value of CTSW in PDAC.


Assuntos
Carcinoma Ductal Pancreático , MicroRNAs , Neoplasias Pancreáticas , Humanos , Catepsina W/genética , Catepsina W/metabolismo , Regulação para Baixo , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patologia , Prognóstico , Biomarcadores , Regulação Neoplásica da Expressão Gênica , Biomarcadores Tumorais/genética , Neoplasias Pancreáticas
8.
Cancers (Basel) ; 15(17)2023 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-37686578

RESUMO

Introduction: Colorectal cancer (CRC) is a common cancer associated with poor outcomes, underscoring a need for the identification of novel prognostic and therapeutic targets to improve outcomes. This study aimed to identify genetic variants and differentially expressed genes (DEGs) using genome-wide DNA and RNA sequencing followed by validation in a large cohort of patients with CRC. Methods: Whole genome and gene expression profiling were used to identify DEGs and genetic alterations in 146 patients with CRC. Gene Ontology, Reactom, GSEA, and Human Disease Ontology were employed to study the biological process and pathways involved in CRC. Survival analysis on dysregulated genes in patients with CRC was conducted using Cox regression and Kaplan-Meier analysis. The STRING database was used to construct a protein-protein interaction (PPI) network. Moreover, candidate genes were subjected to ML-based analysis and the Receiver operating characteristic (ROC) curve. Subsequently, the expression of the identified genes was evaluated by Real-time PCR (RT-PCR) in another cohort of 64 patients with CRC. Gene variants affecting the regulation of candidate gene expressions were further validated followed by Whole Exome Sequencing (WES) in 15 patients with CRC. Results: A total of 3576 DEGs in the early stages of CRC and 2985 DEGs in the advanced stages of CRC were identified. ASPHD1 and ZBTB12 genes were identified as potential prognostic markers. Moreover, the combination of ASPHD and ZBTB12 genes was sensitive, and the two were considered specific markers, with an area under the curve (AUC) of 0.934, 1.00, and 0.986, respectively. The expression levels of these two genes were higher in patients with CRC. Moreover, our data identified two novel genetic variants-the rs925939730 variant in ASPHD1 and the rs1428982750 variant in ZBTB1-as being potentially involved in the regulation of gene expression. Conclusions: Our findings provide a proof of concept for the prognostic values of two novel genes-ASPHD1 and ZBTB12-and their associated variants (rs925939730 and rs1428982750) in CRC, supporting further functional analyses to evaluate the value of emerging biomarkers in colorectal cancer.

9.
Curr Med Chem ; 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37724673

RESUMO

The application of the CRISPR-associated nuclease 9 (Cas9) system in tumor studies has led to the discovery of several new treatment strategies for colorectal cancer (CRC), including the recognition of novel target genes, the construction of animal mass models, and the identification of genes related to chemotherapy resistance. CRISPR/Cas9 can be applied to genome therapy for CRC, particularly regarding molecular-targeted medicines and suppressors. This review summarizes some aspects of using CRISPR/Cas9 in treating CRC. Further in-depth and systematic research is required to fully realize the potential of CRISPR/Cas9 in CRC treatment and integrate it into clinical practice.

10.
Cytokine Growth Factor Rev ; 73: 101-113, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37573251

RESUMO

There is a complex interaction between pro-tumoural and anti-tumoural networks in the tumour microenvironment (TME). Throughout tumourigenesis, communication between malignant cells and various cells of the TME contributes to metabolic reprogramming. Tumour Dysregulation of metabolic pathways offer an evolutional advantage in the TME and enhance the tumour progression, invasiveness, and metastasis. Therefore, understanding these interactions within the TME is crucial for the development of innovative cancer treatments. Extracellular vesicles (EVs) serve as carriers of various materials that include microRNAs, proteins, and lipids that play a vital role in the communication between tumour cells and non-tumour cells. EVs are actively involved in the metabolic reprogramming process. This review summarized recent findings regarding the involvement of EVs in the metabolic reprogramming of various cells in the TME of gastrointestinal cancers. Additionally, we highlight identified microRNAs involved in the reprogramming process in this group of cancers and explained the abnormal tumour metabolism targeted by exosomal cargos as well as the novel potential therapeutic approaches.


Assuntos
Vesículas Extracelulares , Neoplasias Gastrointestinais , MicroRNAs , Neoplasias , Humanos , Comunicação Celular , Neoplasias/metabolismo , Vesículas Extracelulares/fisiologia , MicroRNAs/genética , Neoplasias Gastrointestinais/metabolismo , Carcinogênese/metabolismo , Microambiente Tumoral
11.
Cancers (Basel) ; 15(15)2023 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-37568755

RESUMO

Cytochrome P450 (CYP450) enzyme has been shown to be expressed in colorectal cancer (CRC) and its dysregulation is linked to tumor progression and a poor prognosis. Here we investigated the therapeutic potential of targeting CYP450 using lopinavir/ritonavir in CRC. The integrative systems biology method and RNAseq were utilized to investigate the differential levels of genes associated with patients with colorectal cancer. The antiproliferative activity of lopinavir/ritonavir was evaluated in both monolayer and 3-dimensional (3D) models, followed by wound-healing assays. The effectiveness of targeting CYP450 was examined in a mouse model, followed by histopathological analysis, biochemical tests (MDA, SOD, thiol, and CAT), and RT-PCR. The data of dysregulation expressed genes (DEG) revealed 1268 upregulated and 1074 down-regulated genes in CRC. Among the top-score genes and dysregulated pathways, CYPs were detected and associated with poor prognosis of patients with CRC. Inhibition of CYP450 reduced cell proliferation via modulating survivin, Chop, CYP13a, and induction of cell death, as detected by AnnexinV/PI staining. This agent suppressed the migratory behaviors of cells by induction of E-cadherin. Moreover, lopinavir/ritonavir suppressed tumor growth and fibrosis, which correlated with a reduction in SOD/thiol levels and increased MDA levels. Our findings illustrated the therapeutic potential of targeting the CYP450 using lopinavir/ritonavir in colorectal cancer, supporting future investigations on this novel therapeutic approach for the treatment of CRC.

12.
Artigo em Inglês | MEDLINE | ID: mdl-37455451

RESUMO

Neuropathic pain is a disabling condition caused by various diseases and can profoundly impact the quality of life. Unfortunately, current treatments often do not produce complete amelioration and can be associated with potential side effects. Recently, herbal drugs have garnered more attention as an alternative or a complementary treatment. In this article, we summarized the results of randomized clinical trials to evaluate the effects of various phytomedicines on neuropathic pain. In addition, we discussed their main bioactive components and potential mechanisms of action to provide a better view of the application of herbal drugs for treating neuropathic pain.

13.
Mol Cell Biochem ; 2023 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-37405534

RESUMO

Pancreatic cancer (PC) has a very high mortality rate globally. Despite ongoing efforts, its prognosis has not improved significantly over the last two decades. Thus, further approaches for optimizing treatment are required. Various biological processes oscillate in a circadian rhythm and are regulated by an endogenous clock. The machinery controlling the circadian cycle is tightly coupled with the cell cycle and can interact with tumor suppressor genes/oncogenes; and can therefore potentially influence cancer progression. Understanding the detailed interactions may lead to the discovery of prognostic and diagnostic biomarkers and new potential targets for treatment. Here, we explain how the circadian system relates to the cell cycle, cancer, and tumor suppressor genes/oncogenes. Furthermore, we propose that circadian clock genes may be potential biomarkers for some cancers and review the current advances in the treatment of PC by targeting the circadian clock. Despite efforts to diagnose pancreatic cancer early, it still remains a cancer with poor prognosis and high mortality rates. While studies have shown the role of molecular clock disruption in tumor initiation, development, and therapy resistance, the role of circadian genes in pancreatic cancer pathogenesis is not yet fully understood and further studies are required to better understand the potential of circadian genes as biomarkers and therapeutic targets.

14.
Curr Cancer Drug Targets ; 23(10): 764-777, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37069719

RESUMO

Colorectal cancer (CRC) is a growing concern worldwide. In recent decades, the incidence of CRC has increased, and this has been attributed to changes in lifestyle. The lack of physical activity, smoking habits, and a diet high in red meat and fat and low in fiber are important aspects of these deleterious changes in lifestyle. The increase in the incidence of CRC has impelled researchers to investigate methods for preventing and treating CRC with greater efficacy and fewer complications. Probiotics are an attractive and potentially promising therapeutic approach. They have been evaluated by a large number of preclinical and clinical studies in recent years, and it has been found that they can play a role in the prevention, treatment, and management of complications of CRC. This review provides a concise summary of the mechanisms of action of probiotics. Furthermore, it focuses on the results of clinical and preclinical studies that evaluated probiotics' effects on CRC management. It also discusses the effects of different strains of probiotics and their combination in CRC treatment.


Assuntos
Neoplasias Colorretais , Probióticos , Humanos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/prevenção & controle , Probióticos/uso terapêutico , Probióticos/farmacologia , Dieta , Fumar
15.
Curr Pharm Des ; 29(10): 748-765, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36892023

RESUMO

Colorectal cancer (CRC) is currently the second most prevalent cancer diagnosed in women and the third most common kind of cancer in men. Despite tremendous efforts and advancements in diagnostic approaches and treatment options, the mortality rate of CRC accounts for around one million each year globally. The five-year survival rate of CRC is reported to be approximately 14 percent for patients diagnosed at an advanced stage. Due to its significant associated mortality and morbidity, diagnostic tools to identify the disease at its early stages are urgently required. Early diagnosis may lead to better outcomes. The gold standard approach for CRC diagnosis is colonoscopy with biopsy. However, it is an invasive process with a risk of complications and discomfort for the patient. Moreover, it is usually performed in symptomatic or high-risk individuals and therefore, asymptomatic patients might be missed. Thus, alternative non-invasive diagnostic techniques are required to improve CRC outcomes. The new era of personalized medicine is identifying novel biomarkers associated with overall survival and clinical outcomes. Recently, liquid biopsy, a minimally invasive analysis of body fluid biomarkers, has gained attention for diagnosis, evaluation of prognosis, and follow-up of patients with CRC. Several previous studies have demonstrated that this novel approach allows for better understanding of CRC tumor biology and leads to an improvement in clinical outcomes. Here, we explain the enrichment and detection methods of circulating biomarkers, including CTCs, ctDNA, miRNA, lncRNA, and circRNA. Furthermore, we provide an overview on their clinical potential as diagnostic, prognostic, and predictive biomarkers for CRC.


Assuntos
Ácidos Nucleicos Livres , Neoplasias Colorretais , Células Neoplásicas Circulantes , Feminino , Humanos , Masculino , Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Células Neoplásicas Circulantes/patologia , Prognóstico
16.
Curr Drug Targets ; 24(4): 300-319, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36642873

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is a common metabolic disorder associated with obesity, diabetes mellitus, dyslipidemia, and cardiovascular disease. A "multiple hit" model has been a widely accepted explanation for the disease's complicated pathogenesis. Despite advances in our knowledge of the processes underlying NAFLD, no conventional pharmaceutical therapy exists. The only currently approved option is to make lifestyle modifications, such as dietary and physical activity changes. The use of medicinal plants in the treatment of NAFLD has recently gained interest. Thus, we review the current knowledge about these agents based on clinical and preclinical studies. Moreover, the association between NAFLD and colorectal cancer (CRC), one of the most common and lethal malignancies, has recently emerged as a new study area. We overview the shared dysregulated pathways and the potential therapeutic effect of herbal medicines for CRC prevention in patients with NAFLD.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Plantas Medicinais , Humanos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Medicina Herbária , Preparações Farmacêuticas , Extratos Vegetais/uso terapêutico
17.
Curr Pharm Des ; 28(36): 2995-3009, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36154599

RESUMO

Colorectal cancer (CRC) is one of the most prevalent cancers globally. Despite recent progress in identifying etiologies and molecular genetics as well as new therapeutic approaches, the clinical outcome of current CRC therapies remains poor. This fact highlights the importance of further understanding underlying mechanisms involved in colorectal tumor initiation and progression. Abnormal metabolic alterations offer an evolutional advantage for CRC tumor cells and enhance their aggressive phenotype. Therefore, dysregulation of cellular metabolism is intricately associated with colorectal tumorigenesis. This review summarizes recent findings regarding the CRC-related changes in cellular metabolic pathways such as glycolysis, tricarboxylic acid cycle, fatty acid oxidation, and mitochondrial metabolism. We describe the oncogenic signaling pathways associated with metabolic dysregulation during malignant transformation and tumor progression. Given the crucial role of metabolic pathway alterations in the pathogenesis of CRC, we provide an overview of novel pharmacological strategies for the treatment of CRC by targeting metabolic and signaling pathways.


Assuntos
Neoplasias Colorretais , Glicólise , Humanos , Glicólise/fisiologia , Neoplasias Colorretais/genética , Redes e Vias Metabólicas , Transformação Celular Neoplásica/metabolismo , Transdução de Sinais
18.
Life Sci ; 305: 120760, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-35787997

RESUMO

Alcohol-associated liver disease (ALD) comprises a spectrum of liver diseases that include: steatosis to alcohol-associated hepatitis, cirrhosis, and ultimately hepatocellular carcinoma. The pathophysiology and potential underlying mechanisms for alcohol-associated liver disease are unclear. Moreover, the treatment of ALD remains a challenge. Intestinal microbiota include bacteria, fungi, and viruses, that are now known to be important in the development of ALD. Alcohol consumption can change the gut microbiota and function leading to liver disease. Given the importance of interactions between intestinal microbiota, alcohol, and liver injury, the gut microbiota has emerged as a potential biomarker and therapeutic target. This review focuses on the potential mechanisms by which the gut microbiota may be involved in the pathogenesis of ALD and explains how this can be translated into clinical management. We discuss the potential of utilizing the gut microbiota signature as a biomarker in ALD patients. Additionally, we present an overview of the prospect of modulating the intestinal microbiota for the management of ALD.


Assuntos
Microbioma Gastrointestinal , Hepatopatias Alcoólicas , Microbiota , Bactérias , Biomarcadores , Microbioma Gastrointestinal/fisiologia , Humanos , Fígado/patologia , Hepatopatias Alcoólicas/patologia , Hepatopatias Alcoólicas/terapia , Estudos Prospectivos
19.
Comb Chem High Throughput Screen ; 25(2): 211-228, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33390101

RESUMO

The precise and exquisite architecture of the retina is directly related to vision. Therefore, any mechanisms associated with disruption of retinal structure could affect the quality of vision. A large number of studies indicated that several cellular and molecular processes are involved in retina pathogenesis. Among different risk factors reported as important players in retina diseases, deregulation of epigenetic contributors has critical roles in the pathogenesis of these diseases. MicroRNAs (miRNAs) are a type of small non-coding RNAs that are involved in various signaling pathways involved in retina diseases. These molecules exert their function by targeting a sequence of cellular and molecular signals. Long-non coding RNAs (lncRNAs) and circular RNAs are other non-coding RNAs, which can exert their regulatory roles via miRNA sponging. In this regard, it has been showed that miRNA sponging could modulate a variety of pathways in retinal diseases. Besides miRNAs, exosomes are other players in the pathogenesis of retinal diseases. Exosomes are biological vectors that could carry their cargos to recipient cells. The cargos of exosomes (i.e., proteins, lncRNAs, miRNAs, and fragments of DNA) change behaviors of host cells. Here, we summarized the roles of miRNAs, miRNAs sponging and exosomes in the pathogenesis of retinal diseases.


Assuntos
Exossomos , MicroRNAs , RNA Longo não Codificante , Doenças Retinianas , Exossomos/genética , Exossomos/metabolismo , Exossomos/patologia , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , Doenças Retinianas/diagnóstico , Doenças Retinianas/genética , Doenças Retinianas/metabolismo , Transdução de Sinais
20.
Front Oncol ; 11: 716831, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35186706

RESUMO

Prostate cancer (P.C.) is one of the most frequent diagnosed cancers among men and the first leading cause of death with an annual incidence of 1.4 million worldwide. Prostate-specific antigen is being used for screening/diagnosis of prostate disease, although it is associated with several limitations. Thus, identification of novel biomarkers is warranted for diagnosis of patients at earlier stages. MicroRNAs (miRNAs) are recently being emerged as potential biomarkers. It has been shown that these small molecules can be circulated in body fluids and prognosticate the risk of developing P.C. Several miRNAs, including MiR-20a, MiR-21, miR-375, miR-378, and miR-141, have been proposed to be expressed in prostate cancer. This review summarizes the current knowledge about possible molecular mechanisms and potential application of tissue specific and circulating microRNAs as diagnosis, prognosis, and therapeutic targets in prostate cancer.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA