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1.
Funct Integr Genomics ; 24(3): 102, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38760573

RESUMO

Cardiovascular disease, specifically heart failure (HF), remains a significant concern in the realm of healthcare, necessitating the development of new treatments and biomarkers. The RNA family consists of various subgroups, including microRNAs, PIWI-interacting RNAs (piRAN) and long non-coding RNAs, which have shown potential in advancing personalized healthcare for HF patients. Recent research suggests that circular RNAs, a lesser-known subgroup of RNAs, may offer a novel set of targets and biomarkers for HF. This review will discuss the biogenesis of circular RNAs, their unique characteristics relevant to HF, their role in heart function, and their potential use as biomarkers in the bloodstream. Furthermore, future research directions in this field will be outlined. The stability of exosomal circRNAs makes them suitable as biomarkers, pathogenic regulators, and potential treatments for cardiovascular diseases such as atherosclerosis, acute coronary syndrome, ischemia/reperfusion injury, HF, and peripheral artery disease. Herein, we summarized the role of circular RNAs and their exosomal forms in HF diseases.


Assuntos
Biomarcadores , Exossomos , Insuficiência Cardíaca , RNA Circular , RNA Circular/genética , RNA Circular/metabolismo , Humanos , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/metabolismo , Biomarcadores/metabolismo , Exossomos/metabolismo , Exossomos/genética , Animais , MicroRNAs/genética , MicroRNAs/metabolismo
2.
Cell Mol Neurobiol ; 44(1): 28, 2024 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-38461204

RESUMO

Clearance of accumulated protein aggregates is one of the functions of autophagy. Recently, a clearer understanding of non-coding RNAs (ncRNAs) functions documented that ncRNAs have important roles in several biological processes associated with the development and progression of neurodegenerative disorders. Subtypes of ncRNA, including microRNA (miRNA), long noncoding RNA (lncRNA), and circular RNA (circRNA), are commonly dysregulated in neurodegenerative disorders such as Alzheimer and Parkinson diseases. Dysregulation of these non-coding RNAs has been associated with inhibition or stimulation of autophagy. Decreased miR-124 led to decreased/increased autophagy in experimental model of Alzheimer and Parkinson diseases. Increased BACE1-AS showed enhanced autophagy in Alzheimer disease by targeting miR-214-3p, Beclin-1, LC3-I/LC3-II, p62, and ATG5. A significant increase in NEAT1led to stimulated autophagy in experimental model of PD by targeting PINK1, LC3-I, LC3-II, p62 and miR-374c-5p. In addition, increased BDNF-AS and SNHG1 decreased autophagy in MPTP-induced PD by targeting miR-125b-5p and miR-221/222, respectively. The upregulation of circNF1-419 and circSAMD4A resulted in an increased autophagy by regulating Dynamin-1 and miR-29c 3p, respectively. A detailed discussion of miRNAs, circRNAs, and lncRNAs in relation to their autophagy-related signaling pathways is presented in this study.


Assuntos
Doença de Alzheimer , MicroRNAs , Doenças Neurodegenerativas , Doença de Parkinson , RNA Longo não Codificante , Humanos , Doença de Parkinson/genética , Doença de Parkinson/metabolismo , Secretases da Proteína Precursora do Amiloide , Doença de Alzheimer/genética , Ácido Aspártico Endopeptidases , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Autofagia/genética
3.
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
4.
Neurochem Res ; 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38918332

RESUMO

Neuropsychiatric and neurological disorders pose a significant global health burden, highlighting the need for innovative therapeutic approaches. Fingolimod (FTY720), a common drug to treat multiple sclerosis, has shown promising efficacy against various neuropsychiatric and neurological disorders. Fingolimod exerts its neuroprotective effects by targeting multiple cellular and molecular processes, such as apoptosis, oxidative stress, neuroinflammation, and autophagy. By modulating Sphingosine-1-Phosphate Receptor activity, a key regulator of immune cell trafficking and neuronal function, it also affects synaptic activity and strengthens memory formation. In the hippocampus, fingolimod decreases glutamate levels and increases GABA levels, suggesting a potential role in modulating synaptic transmission and neuronal excitability. Taken together, fingolimod has emerged as a promising neuroprotective agent for neuropsychiatric and neurological disorders. Its broad spectrum of cellular and molecular effects, including the modulation of apoptosis, oxidative stress, neuroinflammation, autophagy, and synaptic plasticity, provides a comprehensive therapeutic approach for these debilitating conditions. Further research is warranted to fully elucidate the mechanisms of action of fingolimod and optimize its use in the treatment of neuropsychiatric and neurological disorders.

5.
Neurochem Res ; 49(3): 583-596, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38114727

RESUMO

Neurological disorders are a major group of non-communicable diseases affecting quality of life. Non-Coding RNAs (ncRNAs) have an important role in the etiology of neurological disorders. In studies on the genesis of neurological diseases, aquaporin 4 (AQP4) expression and activity have both been linked to ncRNAs. The upregulation or downregulation of several ncRNAs leads to neurological disorder progression by targeting AQP4. The role of ncRNAs and AQP4 in neurological disorders is discussed in this review.


Assuntos
MicroRNAs , Doenças do Sistema Nervoso , Humanos , Aquaporina 4/genética , Aquaporina 4/metabolismo , Qualidade de Vida , RNA não Traduzido/metabolismo , Doenças do Sistema Nervoso/genética , Regulação para Baixo
6.
Mol Biol Rep ; 51(1): 741, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38874869

RESUMO

Gastrointestinal cancer is the most fatal cancer worldwide. The etiology of gastrointestinal cancer has yet to be fully characterized. Alcohol consumption, obesity, tobacco, Helicobacter pylori and gastrointestinal disorders, including gastroesophageal reflux disease, gastric ulcer, colon polyps and non-alcoholic fatty liver disease are among the several risks factors for gastrointestinal cancers. Phycocyanin which is abundant in Spirulina. Phycocyanin, a member of phycobiliprotein family with intense blue color, is an anti-diabetic, neuroprotective, anti-oxidative, anti-inflammatory, and anticancer compound. Evidence exists supporting that phycocyanin has antitumor effects, exerting its pharmacological effects by targeting a variety of cellular and molecular processes, i.e., apoptosis, cell-cycle arrest, migration and Wnt/ß-catenin signaling. Phycocyanin has also been applied in treatment of several gastrointestinal disorders such as, gastric ulcer, ulcerative colitis and fatty liver that is known as a risk factor for progression to cancer. Herein, we summarize various cellular and molecular pathways that are affected by phycocyanin, its efficacy upon combined drug treatment, and the potential for nanotechnology in its gastrointestinal cancer therapy.


Assuntos
Neoplasias Gastrointestinais , Ficocianina , Humanos , Ficocianina/farmacologia , Ficocianina/uso terapêutico , Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias Gastrointestinais/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Gastroenteropatias/tratamento farmacológico , Gastroenteropatias/metabolismo
7.
Prep Biochem Biotechnol ; : 1-25, 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38909284

RESUMO

Proteases, enzymes that hydrolyze peptide bonds, have various applications in medicine, clinical applications, and pharmaceutical development. They are used in cancer treatment, wound debridement, contact lens cleaning, prion degradation, biofilm removal, and fibrinolytic agents. Proteases are also crucial in cardiovascular disease treatment, emphasizing the need for safe, affordable, and effective fibrinolytic drugs. Proteolytic enzymes and protease biosensors are increasingly used in diagnostic and therapeutic applications. Advanced technologies, such as nanomaterials-based sensors, are being developed to enhance the sensitivity, specificity, and versatility of protease biosensors. These biosensors are becoming effective tools for disease detection due to their precision and rapidity. They can detect extracellular and intracellular proteases, as well as fluorescence-based methods for real-time and label-free detection of virus-related proteases. The active utilization of proteolytic enzymatic biosensors is expected to expand significantly in biomedical research, in-vitro model systems, and drug development. We focused on journal articles and books published in English between 1982 and 2024 for this study.

8.
Mol Cancer ; 22(1): 183, 2023 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-37974170

RESUMO

Chimeric antigen receptor (CAR) NK and T cell therapy are promising immunotherapeutic approaches for the treatment of cancer. However, the efficacy of CAR NK/T cell therapy is often hindered by various factors, including the phenomenon of trogocytosis, which involves the bidirectional exchange of membrane fragments between cells. In this review, we explore the role of trogocytosis in CAR NK/T cell therapy and highlight potential strategies for its modulation to improve therapeutic efficacy. We provide an in-depth analysis of trogocytosis as it relates to the fate and function of NK and T cells, focusing on its effects on cell activation, cytotoxicity, and antigen presentation. We discuss how trogocytosis can mediate transient antigen loss on cancer cells, thereby negatively affecting the effector function of CAR NK/T cells. Additionally, we address the phenomenon of fratricide and trogocytosis-associated exhaustion, which can limit the persistence and effectiveness of CAR-expressing cells. Furthermore, we explore how trogocytosis can impact CAR NK/T cell functionality, including the acquisition of target molecules and the modulation of signaling pathways. To overcome the negative effects of trogocytosis on cellular immunotherapy, we propose innovative approaches to modulate trogocytosis and augment CAR NK/T cell therapy. These strategies encompass targeting trogocytosis-related molecules, engineering CAR NK/T cells to resist trogocytosis-induced exhaustion and leveraging trogocytosis to enhance the function of CAR-expressing cells. By overcoming the limitations imposed by trogocytosis, it may be possible to unleash the full potential of CAR NK/T therapy against cancer. The knowledge and strategies presented in this review will guide future research and development, leading to improved therapeutic outcomes in the field of immunotherapy.


Assuntos
Neoplasias , Receptores de Antígenos Quiméricos , Humanos , Células Matadoras Naturais , Trogocitose , Imunoterapia Adotiva , Linfócitos T , Receptores de Antígenos Quiméricos/metabolismo , Neoplasias/metabolismo , Terapia Baseada em Transplante de Células e Tecidos
9.
Microb Pathog ; 180: 106130, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37121524

RESUMO

Currently, there are two vaccines based on killed and/or weakened Salmonella bacteria, but no recombinant vaccine is available for preventing or treating the disease. We used an in silico approach to design a multi-epitope vaccine against Salmonella using OmpA, OmpS, SopB, SseB, SthA and FilC antigens. We predicted helper T lymphocyte, cytotoxic T lymphocyte, and IFN-γ epitopes. The FilC sequence was used as a bovine TLR5 agonist, and the linkers KK, AAY, GPGPG and EAAAK were used to connect epitopes. The final sequence consisted of 747 amino acid residues, and the expressed soluble protein (∼79.6 kDa) was predicted to be both non-allergenic and antigenic. The tertiary structure of modeled protein was refined and validated, and the interactions of vaccine 3D structure were evaluated using molecular docking, and molecular dynamics simulation (RMSD, RMSF and Gyration). This structurally stable protein could interact with human TLR5. The C-ImmSim server predicted that this proposed vaccine likely induces an immune response by stimulating T and B cells, making it a potential candidate for further evaluation for the prevention and treatment of Salmonella infection.


Assuntos
Receptor 5 Toll-Like , Fatores de Virulência , Animais , Bovinos , Humanos , Simulação de Acoplamento Molecular , Epitopos de Linfócito T , Epitopos de Linfócito B , Vacinas de Subunidades Antigênicas , Salmonella/genética , Biologia Computacional
10.
Cell Mol Neurobiol ; 43(2): 585-603, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35411434

RESUMO

Glioblastoma (GBM) is the most frequent malignancy among primary brain tumors in adults and one of the worst 5-year survival rates (< 7%) among all human cancers. Till now, treatments that target particular cell or intracellular metabolism have not improved patients' survival. GBM recruits healthy brain cells and subverts their processes to create a microenvironment that contributes to supporting tumor progression. This microenvironment encompasses a complex network in which malignant cells interact with each other and with normal and immune cells to promote tumor proliferation, angiogenesis, metastasis, immune suppression, and treatment resistance. Communication can be direct via cell-to-cell contact, mainly through adhesion molecules, tunneling nanotubes, gap junctions, or indirect by conventional paracrine signaling by cytokine, neurotransmitter, and extracellular vesicles. Understanding these communication routes could open up new avenues for the treatment of this lethal tumor. Hence, therapeutic approaches based on glioma cells` communication have recently drawn attention. This review summarizes recent findings on the crosstalk between glioblastoma cells and their tumor microenvironment, and the impact of this conversation on glioblastoma progression. We also discuss the mechanism of communication of glioma cells and their importance as therapeutic targets and diagnostic and prognostic biomarkers. Overall, understanding the biological mechanism of specific interactions in the tumor microenvironment may help in predicting patient prognosis and developing novel therapeutic strategies to target GBM.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Glioma , Adulto , Humanos , Glioblastoma/patologia , Neoplasias Encefálicas/patologia , Citocinas , Microambiente Tumoral
11.
Mol Cell Biochem ; 478(1): 23-37, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35708866

RESUMO

Liver cancer is the sixth common cancer and forth cause of cancer-related death worldwide. Based on usually advanced stages of hepatocellular carcinoma (HCC) at the time of diagnosis, therapeutic options are limited and, in many cases, not effective, and typically result in the tumor recurrence with a poor prognosis. Radioimmunotherapy (RIT) offers a selective internal radiation therapy approach using beta or alpha emitting radionuclides conjugated with tumor-specific monoclonal antibodies (mAbs), or specific selective peptides. When compared to chemotherapy or radiotherapy, radiolabeled mAbs against cancer-associated antigens could provide a high therapeutic and exclusive radiation dose for cancerous cells while decreasing the exposure-induced side effects to healthy tissues. The recent advances in cancer immunotherapy, such as blockade of immune-checkpoint inhibitors (ICIs), has changed the landscape of cancer therapy, and the efficacy of different classes of immunotherapy has been tested in many clinical trials. Taking into account the use of ICIs in the liver tumor microenvironment, combined therapies with different approaches may enhance the outcome in the future clinical studies. With the development of novel immunotherapy treatment options in the recent years, there has been a great deal of information about combining the diverse treatment modalities to boost the effectiveness of immunomodulatory drugs. In this opinion review, we will discuss the recent advancements in RIT. The current status of immunotherapy and internal radiotherapy will be updated, and we will propose novel approaches for the combination of both techniques. Potential target antigens for radioimmunotherapy in Hepatocellular carcinoma (HCC). HCC radioimmunotherapy target antigens are the most specific and commonly accessible antigens on the surface of HCC cells. CTLA-4 ligand and receptor, TAMs, PD-1/PD-L, TIM-3, specific IEXs/TEXs, ROBO1, and cluster of differentiation antigens CD105, CD147 could all be used in HCC radioimmunotherapy. Abbreviations: TAMs, tumor-associated macrophages; CTLA-4, cytotoxic T-lymphocyte associated antigen-4; PD-1, Programmed cell death protein 1; PD-L, programmed death-ligand1; TIM-3, T-cell immunoglobulin (Ig) and mucin-domain containing protein-3; IEXs, immune cell-derived exosomes; TEXs, tumor-derived exosomes.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/radioterapia , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/metabolismo , Antígeno CTLA-4 , Receptor de Morte Celular Programada 1/metabolismo , Receptor Celular 2 do Vírus da Hepatite A , Radioimunoterapia , Proteínas do Tecido Nervoso , Receptores Imunológicos , Imunoterapia/métodos , Microambiente Tumoral
12.
Crit Rev Food Sci Nutr ; 63(22): 5488-5505, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-34978223

RESUMO

Although conventional drugs are widely used in the prevention and treatment of cardiovascular disease (CVD), they are being used less frequently due to concerns about possible side effects over the long term. There has been a renewed research interest in medicinal plant products, and their role in protecting the cardiovascular system and treating CVD, which are now being considered as potential alternatives to modern drugs. The most important mechanism causing damage to the myocardium after heart attack and reperfusion, is increased levels of free radicals and oxidative stress. Therefore, treatment approaches often focus on reducing free radicals or enhancing antioxidant defense mechanism. It has been previously reported that bioactive natural products can protect the heart muscle in myocardial infarction (MI). Since these compounds are readily available in fruits and vegetables, they could prevent the risk of MI if they are consumed daily. Although the benefits of a healthy diet are well known, many scientific studies have focused on whether pure natural compounds can prevent and treat MI. In this review we summarize the effects of curcumin, resveratrol, quercitin, berberine, and tanshinone on MI and CVD, and focus on their proposed molecular mechanisms of action.


Assuntos
Produtos Biológicos , Infarto do Miocárdio , Humanos , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Infarto do Miocárdio/tratamento farmacológico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Resveratrol/farmacologia , Resveratrol/uso terapêutico , Radicais Livres/uso terapêutico
13.
Intervirology ; 66(1): 63-76, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36882006

RESUMO

INTRODUCTION: MicroRNAs, or miRNAs, with regulatory performance in inflammatory responses and infection are the prevalent manifestations of severe coronavirus disease (COVID-19). This study aimed to evaluate whether PBMC miRNAs are diagnostic biomarkers to screen the ICU COVID-19 and diabetic COVID-19 subjects. METHODS: Candidate miRNAs were selected through previous studies, and then the PBMC levels of selected miRNAs (miR-28, miR-31, miR-34a, and miR-181a) were measured via quantitative reverse transcription PCR. The diagnostic value of miRNAs was determined by the receiver operating characteristic (ROC) curve. The bioinformatics analysis was utilized to predict the DEM genes and relevant bio-functions. RESULTS: The COVID-19 patients admitted to ICU had significantly greater levels of selected miRNAs compared to non-hospitalized COVID-19 and healthy people. Besides, the mean miR-28 and miR-34a expression levels in the diabetic COVID-19 group were significantly upregulated when compared with the non-diabetic COVID-19 group. ROC analyses demonstrated the role of miR-28, miR-34a, and miR-181a as new biomarkers to discriminate the non-hospitalized COVID-19 group from the COVID-19 patients admitted to ICU samples, and also miR-34a can probably act as a useful biomarker for screening diabetic COVID-19 patients. Using bioinformatics analyses, we found the performance of target transcripts in many bioprocesses and diverse metabolic routes such as the regulation of multiple inflammatory parameters. DISCUSSION: The difference in miRNA expression patterns between the studied groups suggested that miR-28, miR-34a, and miR-181a could be helpful as potent biomarkers for diagnosing and controlling COVID-19.


Assuntos
COVID-19 , Diabetes Mellitus , MicroRNAs , Humanos , Leucócitos Mononucleares , COVID-19/diagnóstico , MicroRNAs/genética , Biomarcadores , Unidades de Terapia Intensiva
14.
Intervirology ; 66(1): 122-135, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37699384

RESUMO

INTRODUCTION: This research aimed to evaluate the specific microRNA (miRNA) including miR-17-5p, miRN-140-3p miR-191-5p, miR-200c-3p, and miR-N367 and cellular factors (p21, SDF-1, XCL1, CCL-2, and IL-2) in controlling replication of human immunodeficiency virus (HIV) in ECs. METHODS: The expression of miRNAs was assessed between healthy control groups and patient groups including ART-naïve HIV, HIV ART, ECs, and coinfection (HIV-HBV and HIV-HCV) via real-time PCR technique. Besides, the expression level of the nef gene and cellular factors were assessed by the ELISA method. The differences in the level of cellular factors and selected miRNAs between study groups were analyzed using the Kruskal-Wallis H or one-way ANOVA test. In addition, the potential of selected miRNAs as biomarkers for discriminating study groups was assessed by the receiver-operator characteristic (ROC) curve analysis. RESULTS: Some miRNAs in ECs, HIV ART, and healthy controls have similar expression patterns, whereas a miRNA expression profile of patient groups significantly differed compared to EC and control groups. According to ROC curve analyses, the miR-17-5p, miR-140-3p miR-191-5p, miR-200c-3p, and miR-N367 can be served as biomarkers for discriminating ECs from ART-naïve HIV-infected groups. There was a significant correlation between some miRNAs and cellular factors/the viral load as well. CONCLUSION: This report demonstrated a differentiation in the expression of selected immunological factors and cellular/viral miRNAs in ECs compared to other patient groups. Some miRNAs and cellular factors are involved in the viral replication control, immune response/modulation and can be used as biomarkers for diagnosis of ECs and differentiation with other groups. Differential expression of these miRNAs and cellular factors in different stages of HIV infection can help in finding novel ways for infection control.


Assuntos
Coinfecção , Infecções por HIV , Hepatite C , MicroRNAs , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Vírus da Hepatite B/genética , Hepacivirus/genética , Infecções por HIV/complicações , HIV , Perfilação da Expressão Gênica/métodos , Biomarcadores , Hepatite C/complicações
15.
Curr Microbiol ; 80(8): 248, 2023 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-37341794

RESUMO

MicroRNAs, or miRNAs, may involve in coagulation and inflammation pathways caused by severe Coronavirus disease (COVID-19). Accordingly, this attempt was made to explore the behavior of peripheral blood mononuclear cells (PBMCs) miRNAs as effective biomarkers to diagnose COVID-19 patients with normal and abnormal coagulation indices. We selected the targeted miRNAs (miR-19a-3p, miR-223-3p, miR-143-5p, miR-494-3p and miR-301a-5p) according to previous reports, whose PBMC levels were then determined by real-time PCR. Receiver operating characteristic (ROC) curve was obtained to clarify the diagnostic potency of studied miRNAs. The differentially expressed miRNA profiles and corresponding biological activities were predicted in accordance with bioinformatics data. Targeted miRNAs' expression profiles displayed a significant difference between COVID-19 subjects with normal and abnormal coagulation indices. Moreover, the average miR-223-3p level expressed in COVID-19 cases with normal coagulation indices was significantly lower than that in healthy controls. Based on data from ROC analysis, miR-223-3p and miR-494-3p are promising biomarkers to distinguish the COVID-19 cases with normal or abnormal coagulation indices. Bioinformatics data highlighted the prominent role of selected miRNAs in the inflammation and TGF-beta signaling pathway. The differences existed in the expression profiles of selected miRNAs between the groups introduced miR-494-3p and miR-223-3p as potent biomarkers to prognosis the incidence of COVID-19.


Assuntos
COVID-19 , MicroRNAs , Humanos , MicroRNAs/genética , Leucócitos Mononucleares , Diagnóstico Diferencial , Perfilação da Expressão Gênica , COVID-19/diagnóstico , Biomarcadores , Inflamação , Teste para COVID-19
16.
Phytother Res ; 37(5): 1968-1985, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36788749

RESUMO

Silybum marianum seeds contain a family of flavonolignans which can regulate cancer cell proliferation and apoptosis. However, research has rarely focused on the effect of S. marianum essential oil in combination with another anticancer drug. Here, we evaluated the antitumor effect of a combination of 5-fluorouracil (5-FU) and S. marianum essential oils on some pathways in hepatocellular carcinoma (HCC) in vitro and in vivo. Gas chromatography-mass spectrography results indicated there was no significant difference between the components of essential oils isolated from two geographical areas (Khuzestan or Isfahan, Sm-K or Sm-I). Each preparation decreased the viability of H22 cells compared to the control group. S. marianum essential oils alone, and combined with 5-FU, reduced the migration and invasion of H22 cells. Angiogenesis-related proteins were significantly reduced both in vivo and in vitro. Apoptosis and autophagy-related proteins were modulated both in vivo and in vitro. Each treatment decreased phospho-NF-κB (p65) and NF-κB (p65) protein levels. Expression levels of Wnt pathway-related genes were also decreased both in vivo and in vitro. Results revealed that the combination of S. marianum and 5-FU prolonged survival in a mouse model of HCC compared to either treatment alone.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Óleos Voláteis , Animais , Camundongos , Carcinoma Hepatocelular/patologia , Silybum marianum , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Neoplasias Hepáticas/patologia , NF-kappa B/metabolismo , Óleos Voláteis/farmacologia , Óleos Voláteis/uso terapêutico , Apoptose
17.
J Immunoassay Immunochem ; 44(3): 229-241, 2023 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-36576143

RESUMO

Probiotics positively influence age-related macular degeneration (ARMD) given their propensity to attenuate oxidative and inflammatory stress. We addressed the impact of probiotics on metabolic profiles, clinical indices, inflammatory and oxidative stress parameters in ARMD patients. We performed a randomized, double-blind, placebo-controlled trial analyzing 57 subjects with ARMD aged between 50 and 85 years. Subjects were randomized into two groups, and received daily for 8 weeks either probiotic capsule or placebo. Fasting blood samples were obtained at baseline and after the 8-week intervention for the determination of metabolic profiles and oxidative stress biomarkers. After the 8-week intervention, compared with the placebo, probiotic supplementation significantly increased means HDL-cholesterol (Probiotic group: +3.86±4.42 vs. Placebo group: -0.55±4.93 mg/dL, P = .001), plasma total antioxidant capacity (TAC) (Probiotic group: +77.43±168.30 vs. Placebo group: -23.12±169.22 mmol/L, P = .02) and significantly decreased malondialdehyde (MDA) levels (Probiotic group: -0.18±0.46 vs. Placebo group: +0.18±0.25 µmol/L, P = .001). There was no significant effect of probiotic administration on other metabolic profiles and clinical symptoms. Overall, an eight-week probiotic administration among ARMD patients had beneficial effects on TAC, MDA and HDL-cholesterol levels; however, it did not affect clinical signs and other metabolic profiles.


Assuntos
Proteína C-Reativa , Probióticos , Humanos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Probióticos/farmacologia , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Biomarcadores , Colesterol
18.
Semin Cancer Biol ; 69: 24-42, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-31870939

RESUMO

Cancer is known as one of the most common diseases that are associated with high mobility and mortality in the world. Despite several efforts, current cancer treatment modalities often are highly toxic and lack efficacy and specificity. However, the application of nanotechnology has led to the development of effective nanosized drug delivery systems which are highly selective for tumors and allow a slow release of active anticancer agents. Different Nanoparticles (NPs) such as the silicon-based nano-materials, polymers, liposomes and metal NPs have been designed to deliver anti-cancer drugs to tumor sites. Among different drug delivery systems, carbohydrate-functionalized nanomaterials, specially based on their multi-valent binding capacities and desirable bio-compatibility, have attracted considerable attention as an excellent candidate for controlled release of therapeutic agents. In addition, these carbohydrate functionalized nano-carriers are more compatible with construction of the intracellular delivery platforms like the carbohydrate-modified metal NPs, quantum dots, and magnetic nano-materials. In this review, we discuss recent research in the field of multifunctional glycol-nanoparticles (GNPs) intended for cancer drug delivery applications.


Assuntos
Antineoplásicos/uso terapêutico , Carboidratos/química , Sistemas de Liberação de Medicamentos , Nanopartículas/administração & dosagem , Nanotecnologia/métodos , Neoplasias/tratamento farmacológico , Polímeros/química , Animais , Humanos , Nanopartículas/química , Pontos Quânticos
19.
Dev Biol ; 475: 37-53, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33684433

RESUMO

In recent years, the development of 3D organoids has opened new avenues of investigation into development, physiology, and regenerative medicine. Organoid formation and the process of organogenesis share common developmental pathways; thus, our knowledge of developmental biology can help model the complexity of different organs to refine organoids into a more sophisticated platform. The developmental process is strongly dependent on complex networks and communication of cell-cell and cell-matrix interactions among different cell populations and their microenvironment, during embryogenesis. These interactions affect cell behaviors such as proliferation, survival, migration, and differentiation. Co-culture systems within the organoid technology were recently developed and provided the highly physiologically relevant systems. Supportive cells including various types of endothelial and stromal cells provide the proper microenvironment, facilitate organoid assembly, and improve vascularization and maturation of organoids. This review discusses the role of the co-culture systems in organoid generation, with a focus on how knowledge of developmental biology has directed and continues to shape the development of more evolved 3D co-culture system-derived organoids.


Assuntos
Técnicas de Cultura de Células/métodos , Técnicas de Cocultura/métodos , Organoides/crescimento & desenvolvimento , Animais , Técnicas de Cultura de Células/tendências , Diferenciação Celular , Técnicas de Cocultura/tendências , Biologia do Desenvolvimento/tendências , Humanos , Organogênese , Organoides/citologia , Organoides/metabolismo
20.
Cell Mol Neurobiol ; 42(8): 2449-2457, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34283340

RESUMO

Parkinson's disease (PD) is a progressive neurological disorder characterized by motor and non-motor features. Although some progress has been made in conventional PD treatments, these breakthroughs have yet to show high efficacy in treating this neurodegenerative disease. Probiotics are live microorganisms that confer health benefits on the host when administered in adequate amounts. Probiotics have putative anticancer, antioxidative, anti-inflammatory, and neuroprotective effects. Multiple lines of evidence show that probiotics control and improve several motor and non-motor symptoms in patients and experimental animal models of PD. Probiotic supplementation mediates these pharmacological effects by targeting a variety of cellular and molecular processes, i.e., oxidative stress, inflammatory and anti-inflammatory pathways, as well as apoptosis. Herein, we summarize the effects of probiotics on motor and non-motor symptoms as well as various cellular and molecular pathways in PD.


Assuntos
Doenças Neurodegenerativas , Fármacos Neuroprotetores , Doença de Parkinson , Probióticos , Animais , Anti-Inflamatórios/uso terapêutico , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Probióticos/uso terapêutico
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