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1.
Toxicol Ind Health ; 38(11): 717-732, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36180968

RESUMO

In this study, oxidative stress was investigated as the possible mechanism of action of organochlorine pesticides (OCPs) and organophosphorus pesticides (OPPs) in primary brain tumors (PBT). The levels of seven OCP residues and enzymatic antioxidant biomarkers including erythrocyte acetylcholinesterase (AChE), superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), and paraoxonase-1 (PON-1) along with non-enzymatic oxidative biomarkers including malondialdehyde (MDA), protein carbonyl (PC), total antioxidant capacity (TAC), and nitric oxide (NO) were measured in blood samples of 73 patients with PBT and 104 healthy controls. A significant association was found between farming activities and PBT (55% of patients were engaged in farming activities while 45% had no farming experience). The mean levels of ß-HCH, γ-HCH, 2,4 DDE, 4,4 DDE, 4,4 DDT, MDA, PC, NO, SOD, CAT, and GPx were significantly higher in PBT patients, whereas the levels of TAC, PON-1, and AChE were significantly lower in these patients. Regression analysis showed that PBT was correlated with ß-HCH, γ-HCH, 2,4 DDE, 4,4 DDE, and 4,4 DDT. Based on these results, it can be concluded that OCPs and OPPs may play a role in PBT development through the formation of reactive oxygen species (ROS) and promoting oxidative stress.


Assuntos
Neoplasias Encefálicas , Hidrocarbonetos Clorados , Praguicidas , Humanos , Praguicidas/toxicidade , Hexaclorocicloexano/análise , Compostos Organofosforados/toxicidade , Catalase , Acetilcolinesterase , Espécies Reativas de Oxigênio , Antioxidantes/análise , Arildialquilfosfatase , Glutationa Peroxidase , Óxido Nítrico , DDT , Diclorodifenil Dicloroetileno/análise , Hidrocarbonetos Clorados/toxicidade , Estresse Oxidativo , Malondialdeído , Neoplasias Encefálicas/induzido quimicamente , Biomarcadores , Superóxido Dismutase
2.
Cytokine ; 148: 155706, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34583254

RESUMO

Multiple sclerosis (MS) is a specific type of chronic immune-mediated disease in which the immune responses are almost run against the central nervous system (CNS). Despite intensive research, a known treatment for MS disease yet to be introduced. Thus, the development of novel and safe medications needs to be considered for the disease management. Application of mesenchymal stem cells (MSCs) as an emerging approach was recruited forthe treatment of MS. MSCs have several sources and they can be derived from the umbilical cord, adipose tissue, and bone marrow. Chemokines are low molecular weight proteins that their functional activities are achieved by binding to the cell surface G protein-coupled receptors (GPCRs). Chemokine and chemokine receptors are of the most important and effective molecules in MSC trafficking within the different tissues in hemostatic and non-hemostatic circumstances. Chemokine/chemokine receptor axes play a pivotal role in the recruitment and oriented trafficking of immune cells both towards and within the CNS and it appears that chemokine/chemokine receptor signaling may be the most important leading mechanisms in the pathogenesis of MS. In this article, we hypothesized that the chemokine/chemokine receptor axes network have crucial and efficacious impacts on behavior of the MSCs, nonetheless, the exact responsibility of these axes on the targeted tropism of MSCs to the CNS of MS patients yet remained to be fully elucidated. Therefore, we reviewed the ability of MSCs to migrate and home into the CNS of MS patients via expression of various chemokine receptors in response to chemokines expressed by cells of CNS tissue, to provide a great source of knowledge.


Assuntos
Movimento Celular , Quimiocinas/metabolismo , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/patologia , Esclerose Múltipla/patologia , Receptores de Quimiocinas/metabolismo , Animais , Humanos , Modelos Biológicos
3.
Cytokine ; 144: 155545, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33965313

RESUMO

BACKGROUND: Coronary artery disease (CAD) is the world's largest cause of death. The association of CAD with inflammation is well established. Recently, it has been confirmed that the C1q/TNF-related protein 12 (CTRP12) has a great anti-inflammatory effect. However, few data are available regarding the serum CTRP12 concentration levels in CAD patients. OBJECTIVE: The study was performed to evaluate the correlation between the serum levels of CTRP12 and the CAD severity regarding to the number of affected vessels. METHODS: About 200 suspected CAD patients and 50 healthy ones as a control, were evaluated based on case-control study. According to the results of angiography, patients were divided into CAD+ (n = 150) with any major coronary artery stenosis ≥50% and CAD- (n = 50) with <50% stenosis of the arteries. The CAD+patients were categorized into one- (1VD), two- (2VD) and three-vessel disease (3VD) based on the number of stenotic vessels. In the current study, different parameters such as CTRP12, tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), total oxidant status (TOS), total antioxidant capacity (TAC), and malondialdehyde (MDA) levels were evaluated, and also lipid profiles, hs-CRP and demographic factors were investigated as well. RESULTS: Data revealed that CTRP12 and TAC levels in CAD + group were significantly lower than control subjects (P < 0.05). CTRP12 levels were found to be significantly lower in the 3VD compared with 1VD and 2VD subgroups (p < 0.01 and p < 0.05, respectively). CONCLUSION: Our results confirmed that serum CTRP12 level is inversely associated with CAD severity. Therefore, it may be used as a prediction marker for CAD.


Assuntos
Adipocinas/metabolismo , Complemento C1q/metabolismo , Doença da Artéria Coronariana/metabolismo , Antioxidantes/metabolismo , Biomarcadores/metabolismo , Estudos de Casos e Controles , Angiografia Coronária/métodos , Feminino , Humanos , Inflamação/metabolismo , Masculino , Malondialdeído/metabolismo , Pessoa de Meia-Idade , Fatores de Risco , Índice de Gravidade de Doença
4.
Gynecol Oncol ; 161(1): 314-327, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33581845

RESUMO

Gynecologic cancer is a group of any malignancies affecting reproductive tissues and organs of women, including ovaries, uterine, cervix, vagina, vulva, and endometrium. Several types of molecular mechanisms are associated with the progression of gynecologic cancers. Among it can be referred to the most widely studied non-coding RNAs (ncRNAs), specifically microRNAs (miRNAs) and long ncRNAs (lncRNAs). As yet, lncRNAs are known to serve key biological roles via various mechanisms, such as splicing regulation, chromatin rearrangement, translation regulation, cell-cycle control, genetic imprinting and mRNA decay. Besides, miRNAs govern gene expression by modulation of mRNAs and lncRNAs degradation, suggestive of needing more research in this field. Generally, driving gynecological cancers pathways by miRNAs and lncRNAs lead to the current improvement in cancer-related technologies. Exosomes are extracellular microvesicles which can carry cargo molecules among cells. In recent years, more studies have been focused on exosomal non-coding RNAs (exo-ncRNAs) and exosomal microRNAs (exo-miRs) because of being natural carriers of lnc RNAs and microRNAs via programmed process. In this review we summarized recent reports concerning the function of exosomal microRNAs and exosomal long non-coding RNAs in gynecological cancers.


Assuntos
Exossomos/genética , Neoplasias dos Genitais Femininos/genética , RNA Longo não Codificante/genética , Exossomos/metabolismo , Feminino , Neoplasias dos Genitais Femininos/metabolismo , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo
5.
Adv Exp Med Biol ; 1328: 143-153, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34981476

RESUMO

Despite newer advances in cancer treatment, chemotherapy is still one of the most widely used treatment strategies in this field. However, this treatment strategy faces major challenges. Doxorubicin (Dox) is an effective chemotherapeutic agent used to treat various cancers. However, several studies have shown that the use of Dox in therapeutic concentrations is associated with serious side effects, such as cardiac toxicity. The use of natural products in combination with chemotherapeutic agents to reduce side effects is a novel approach, and several studies have shown promising results. In this regard, we examined the effect of Crocin on doxorubicin-induced cardiotoxicity in rat and H9c2 cell line. The in vitro model on H9C2 cells and the in vivo models on rats were treated with doxorubicin. Cell viability, DNA damage, and apoptosis were measured in H9C2 cell line in the presence and absence of Crocin. Oxidative stress and various inflammatory parameters, as well as cardiac function tests, also were assessed in doxorubicin-induced cardiotoxicity animal model in the presence and absence of Crocin. Our results showed that Crocin can significantly decrease apoptosis in H9C2 cell line through a reduction in ROS production and DNA damages. Moreover, evaluation of the effect of Crocin on doxorubicin-induced cardiotoxicity animal model showed that Crocin also can significantly reduce oxidative stress and inflammatory parameters in the serum of the animals. Assessment of cardiac function revealed that Crocin has a significant protective effect against doxorubicin-induced cardiotoxicity in the animal model. Our data indicate that Crocin significantly attenuated doxorubicin-induced cardiotoxicity. Hence, Crocin could be potentially used as an adjuvant treatment in combination with Dox to reduce cardiotoxicity.


Assuntos
Cardiotoxicidade , Doxorrubicina , Animais , Apoptose , Cardiotoxicidade/prevenção & controle , Carotenoides/metabolismo , Carotenoides/farmacologia , Doxorrubicina/toxicidade , Miócitos Cardíacos/metabolismo , Estresse Oxidativo , Ratos
6.
J Basic Microbiol ; 60(5): 435-443, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32128846

RESUMO

Chemical pesticides or insecticides with complex structures are highly abundant in the biosphere and have inevitable side effects on farmland, natural resources, and human health. Deltamethrin is the most popular and widely used pesticide that disrupts the cellular calcium channels. In the present study, isolated strains of bacteria were examined to determine the ones that were capable of degrading deltamethrin. Different species of bacteria were evaluated in terms of the capability to degrade deltamethrin. It is important to note that Streptomyces rimosus was able to degrade up to 200 mg/L deltamethrin concentration and could be grown in mineral salt medium agar containing deltamethrin to be used as a source of carbon and energy. The results demonstrated that there is a diversity of deltamethrin-degrading bacteria in agricultural soil ecosystems. The application of these bacteria, especially S. rimosus, might be used as a bioremediation technique to decrease pesticide contamination of the ecosystem.


Assuntos
Nitrilas/metabolismo , Praguicidas/metabolismo , Piretrinas/metabolismo , Poluentes do Solo/metabolismo , Streptomyces rimosus/isolamento & purificação , Streptomyces rimosus/metabolismo , Agricultura , Bactérias/classificação , Bactérias/crescimento & desenvolvimento , Bactérias/isolamento & purificação , Bactérias/metabolismo , Biodegradação Ambiental , Biodiversidade , Solo/química , Microbiologia do Solo , Streptomyces rimosus/classificação , Streptomyces rimosus/crescimento & desenvolvimento
7.
J Cell Physiol ; 234(6): 8465-8486, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30515779

RESUMO

Leukemia is known as a progressive malignant disease, which destroys the blood-forming organs and results in adverse effects on the proliferation and development of leukocytes and their precursors in the blood and bone marrow. There are four main classes of leukemia including acute leukemia, chronic leukemia, myelogenous leukemia, and lymphocytic leukemia. Given that a variety of internal and external factors could be associated with the initiation and progression of different types of leukemia. One of the important factors is epigenetic regulators such as microRNAs (miRNAs) and long noncoding RNAs (ncRNA). MiRNAs are short ncRNAs which act as tumor suppressor (i.e., miR-15, miR-16, let-7, and miR-127) or oncogene (i.e., miR-155, miR-17-92, miR-21, miR-125b, miR-93, miR-143-p3, miR-196b, and miR-223) in leukemia. It has been shown that deregulation of these molecules are associated with the initiation and progression of leukemia. Hence, miRNAs could be used as potential therapeutic candidates in the treatment of patients with leukemia. Moreover, increasing evidence revealed that miRNAs could be used as diagnostic and prognostic biomarkers in monitoring patients in early stages of disease or after received chemotherapy regimen. It seems that identification and development of new miRNAs could pave to the way to the development new therapeutic platforms for patients with leukemia. Here, we summarized various miRNAs as tumor suppressor and oncogene which could be introduced as therapeutic targets in treatment of leukemia.


Assuntos
Genes Supressores de Tumor , Leucemia/genética , MicroRNAs/genética , Oncogenes/genética , Epigênese Genética/genética , Humanos , Leucemia/patologia , Leucemia/terapia
8.
J Cell Biochem ; 120(9): 14875-14884, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31016763

RESUMO

Cholestatic liver disease is recognized by extreme collagen formation and deposition, which is mediated by free radicals. The aim of the current study was to investigate the probable hepatoprotective effects of hydroalcoholic extract of watercress (WC) against oxidative stress and liver injury in bile duct ligation (BDL)- induced cholestatic rats. A total of 32 male Wistar rats were divided into four groups; sham control (SC), BDL, SC + hydroalcoholic extract of WC and BDL + hydroalcoholic extract of WC. WC-treated rats received daily WC 500 mg/kg/day for 10 days. Biochemical tests, hepatic oxidative stress markers, and antioxidant enzymes activity were estimated. Further, liver hydroxyproline content was assayed and histological analysis was made. The BDL model markedly elevated the protein carbonyl (PCO) and hydroxyproline contents and decreased the glutathione peroxidase (GPx) activity. Hydroalcoholic extract of WC significantly decreased the surge in liver PCO and hydroxyproline levels and increased the reduced GPx enzyme activity contents in the hepatic tissue. As determined by hematoxylin and eosin staining, BDL considerably induced hepatocyte necrosis. Moreover, these changes were significantly attenuated by the hydroalcoholic extract of WC treatment. Our data indicate that the hydroalcoholic extract of WC extract attenuated liver damage in BDL rats by decreasing the hydroxyproline content and histopathological indexes. Also, it reduced oxidative stress by preventing the hepatic protein oxidation and enhancing the activity of the GPx enzyme via antioxidative effect and free-radical scavenging. Our findings suggest that hydroalcoholic extract of WC could be a beneficial new curative agent for cholestatic liver damage.


Assuntos
Colestase Intra-Hepática/tratamento farmacológico , Hidroxiprolina/análise , Nasturtium/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Antioxidantes/farmacologia , Ductos Biliares/patologia , Glutationa Peroxidase/metabolismo , Fígado/lesões , Masculino , Necrose/tratamento farmacológico , Oxirredução/efeitos dos fármacos , Carbonilação Proteica/efeitos dos fármacos , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo
9.
Iran J Allergy Asthma Immunol ; 22(2): 138-149, 2023 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-37496407

RESUMO

Asthma is an inflammatory disease of the airways. We assessed the anti-inflammatory and antioxidative impacts of quercetin, a plant derivative, on inflammatory and oxidative indices in lung tissue and serum of rats with asthma.Asth ma was induced by ovalbumin. Rats were divided into 4 groups: control, asthma+vehicle (Receieved normal saline), asthma+dexamethasone, and asthma+quercetin. After asthma induction, quercetin (50 mg/kg) and dexamethasone (2.5 mg/kg) were injected intraperitoneally once daily for 1 week. On day 50, lung histopathology indices; inflammatory factors; tissue gene expression, including GATA Binding Protein 3 (Gata-3), Tbx21 (T-bet), Transforming growth factor-ß (TGF-ß), Il10 (IL-10), Il1b (IL-1ß), Il6 (IL-6), Acta2 (α-SMA), and Tnf (TNF-α); and oxidative stress indices (malondialdehyde [MDA], catalase [CAT], glutathione peroxidase [GPX], superoxide dismutase [SOD], and total antioxidant capacity [TAC]) in tissue and serum, were evaluated. The results showed that quercetin reduced Gata3, Tnf, Tgfb1, Il1b, and Acta2 gene expression and increased Tbx21 gene expression following asthma. Quercetin also improved oxidative stress by decreasing MDA levels and increasing TAC, CAT, SOD, and GPX levels in serum and lung tissue. Furthermore, quercetin decreased IL6 and TNFα levels and increased IL10 levels in lung tissue after asthma was treated with quercetin. Quercetin ameliorates oxidative stress and inflammation caused by asthma, especially at the tissue level. Therefore, quercetin can be considered a potent antiasthmatic agent.


Assuntos
Antioxidantes , Asma , Ratos , Animais , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Quercetina/farmacologia , Quercetina/uso terapêutico , Interleucina-10/genética , Interleucina-10/metabolismo , Oxidantes , Interleucina-6/metabolismo , Asma/tratamento farmacológico , Asma/metabolismo , Inflamação/tratamento farmacológico , Estresse Oxidativo , Fator de Necrose Tumoral alfa/metabolismo , Superóxido Dismutase/metabolismo , Dexametasona
10.
J Trace Elem Med Biol ; 79: 127229, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37315393

RESUMO

BACKGROUND: Cisplatin is a prevalent chemotherapeutic agent, and it has been used extensively to treat lung cancer. However, its clinical efficacy is hampered by its safety profile and dose-limiting toxicity. Saffron is a natural product that has shown significant anticancer effects. The combination treatment of saffron with chemotherapeutic agents has been considered a new strategy. METHODS: Herein, saffron extract as a natural anticancer substance was combined with cisplatin to assess their combined efficacy against tumor development in vitro. In A549 and QU-DB cell lines, the combined effect of the saffron extract with cisplatin led to a significant reduction in cell viability as compared to cisplatin alone. RESULTS: After 48 h incubation a considerable reduction in ROS levels in the QU-DB cell line upon treatment with cisplatin in the presence of saffron extract in comparison with cells treated with cisplatin alone. Furthermore, apoptosis increased significantly when in cells treated with cisplatin in combination with saffron extract compared to cisplatin alone. CONCLUSION: Our data establish that the combination of saffron extract as a natural anticancer substance with cisplatin leads to improved cell toxicity of cisplatin as an anticancer agent. Therefore, the saffron extract could be potentially used as an additive to enable a reduction in cisplatin dosages and its side effects.


Assuntos
Antineoplásicos , Crocus , Neoplasias Pulmonares , Humanos , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Linhagem Celular Tumoral , Extratos Vegetais/farmacologia , Apoptose , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia
11.
Cardiology ; 122(4): 203-9, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22854352

RESUMO

OBJECTIVES: We studied the association between the prooxidant-antioxidant balance (PAB), anti-malondialdehyde-modified low-density lipoprotein (oxidized LDL, ox-LDL) IgG antibody and indices of cardiac function (systolic and diastolic function) in patients with coronary artery disease (CAD). METHODS: Fifty-five patients with established CAD were selected, and serum levels of anti-ox-LDL IgG and PAB values were measured and compared with 40 matched healthy controls. Systolic and diastolic functions were determined for all patients. RESULTS: PAB values were significantly higher in patients than in controls (p < 0.001), whilst serum anti-ox-LDL concentrations were not statistically different between the 2 groups (p = 0.821). However, after adjustment for high-density lipoprotein cholesterol, the patients had higher anti-ox-LDL levels (p = 0.04). Total PAB values were inversely associated with ejection fraction (r = -0.326, p = 0.031), but this was not the case for anti-ox-LDL in either group (p > 0.05). CONCLUSION: Serum concentrations of a marker of oxidative stress (PAB values) are inversely associated with cardiac function. PAB is a relatively simple index that could be incorporated into risk assessment in CAD patients. Anti-ox-LDL IgG antibody concentration does not appear to reflect total oxidative stress as assessed by PAB.


Assuntos
Anticorpos/metabolismo , Antioxidantes/metabolismo , Doença da Artéria Coronariana/fisiopatologia , Imunoglobulina G/metabolismo , Lipoproteínas LDL/imunologia , Biomarcadores/metabolismo , Doença da Artéria Coronariana/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/imunologia , Espécies Reativas de Oxigênio/metabolismo
12.
Artigo em Inglês | MEDLINE | ID: mdl-35774748

RESUMO

Background: Asthma is known as a disease that causes breathing problems in children and adults and is also associated with chronic inflammation and oxidative stress of the airways. Nasturtium officinale (NO) possesses a wide range of pharmacological properties, particularly anti-inflammation and antioxidant potentials. Thus, this study for the first time was aimed to investigate anti-inflammatory and antioxidative activities of NO extract (NOE) in an ovalbumin-induced rat model of asthma. Materials and Methods: Forty-four male Wistar rats were sensitized with ovalbumin (OVA) to induce asthma symptoms. The animals were allocated into five groups: control (C), asthmatic (A), A + NOE (500 mg/kg), NOE (500 mg/kg), and A + dexamethasone (DX, 2.5 mg/kg). After 7 days, blood and tissue samples were taken from the rats. Then, the level of inflammatory markers, oxidative stress parameters, and antioxidant enzymes activity were measured. Results: The obtained results showed that OVA-sensitive rats significantly increased the levels of pro-inflammatory cytokines IL-1B, TGF-ß, and SMA-α compared to the control group (p < 0.05), while treatment with NOE remarkably reduced the SMA-α gene expression compared to the asthma group (p < 0.05). Furthermore, it decreased the expression of IL-1B and TNF-α genes, although it was not statistically significant. The level of glutathione peroxidase (GPX) significantly reduced in A group compared to the C group (p < 0.05), whereas NOE administration significantly increased this marker (p < 0.05). Moreover, NOE attenuated inflammation and alveolar injury in the lungs of OVA-sensitive rat compared to the nontreated A group. Conclusions: Overall, our findings demonstrated that NOE somewhat is able to reduce airway inflammation by reducing inflammatory and increasing GPX activity. Indeed, further experiments investigating the impact of different extract doses are needed to confirm the antioxidant and anti-inflammatory effects of NOE.

13.
Biomed Pharmacother ; 156: 113889, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36265309

RESUMO

Many questions on the SARS-CoV-2 pathogenesis remain to answer. The SARS-CoV-2 genome encodes some accessory proteins that are essential for infection. Notably, accessory proteins of SARS-CoV-2 play significant roles in affecting immune escape and viral pathogenesis. Therefore SARS-CoV-2 accessory proteins could be considered putative drug targets. IFN-I and IFN-III responses are the primary mechanisms of innate antiviral immunity in infection clearance. Previous research has shown that SARS-CoV-2 suppresses IFN-ß by infecting host cells via ORF3a, ORF3b, ORF6, ORF7a, ORF7b, ORF8, and ORF9b. Furthermore, ORF3a, ORF7a, and ORF7b have a role in blocking IFNα signaling, and ORF8 represses IFNß signaling. The ORF3a, ORF7a, and ORF7b disrupt the STAT1/2 phosphorylation. ORF3a, ORF6, ORF7a, and ORF7b could prevent the ISRE promoter activity. The main SARS-CoV-2 accessory proteins involved in immune evasion are discussed here for comprehensive learning on viral entry, replication, and transmission in vaccines and antiviral development.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Evasão da Resposta Imune , Interferon beta/genética , Antivirais
14.
J Exp Clin Cancer Res ; 41(1): 278, 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36114510

RESUMO

Epithelial-mesenchymal transition (EMT) is a fundamental process for embryonic development during which epithelial cells acquire mesenchymal characteristics, and the underlying mechanisms confer malignant features to carcinoma cells such as dissemination throughout the organism and resistance to anticancer treatments. During the past decades, an entire class of molecules, called non-coding RNA (ncRNA), has been characterized as a key regulator of almost every cellular process, including EMT. Like protein-coding genes, ncRNAs can be deregulated in cancer, acting as oncogenes or tumor suppressors. The various forms of ncRNAs, including microRNAs, PIWI-interacting RNAs, small nucleolar RNAs, transfer RNA-derived RNA fragments, long non-coding RNAs, and circular RNAs can orchestrate the complex regulatory networks of EMT at multiple levels. Understanding the molecular mechanism underlying ncRNAs in EMT can provide fundamental insights into cancer metastasis and may lead to novel therapeutic approaches. In this review, we describe recent advances in the understanding of ncRNAs in EMT and provide an overview of recent ncRNA applications in the clinic.


Assuntos
MicroRNAs , Neoplasias , Transição Epitelial-Mesenquimal/genética , Humanos , MicroRNAs/genética , Neoplasias/genética , Neoplasias/patologia , RNA Circular , RNA não Traduzido/genética
15.
Front Pharmacol ; 13: 970402, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36120349

RESUMO

The present investigation was conducted to evaluate the vascular-toxicity of empagliflozin (EMP) in embryonic vasculature. Firstly, the vascular-toxicity of the drug as well as its interaction with apoptotic regulator proteins was predicted via in silico approach. In the next step, the apoptotic-signaling pathway in embryonic vasculature was evaluated using a chick's YSM model. In silico simulation confirmed vascular-toxicity of EMP. There was also an accurate affinity between EMP, Bax and Bcl-2 (-7.9 kcal/mol). Molecular dynamics assay revealed complex stability in the human body conditions. Furthermore, EMP is suggested to alter Bcl-2 more than BAX. Morphometric quantification of the vessels showed that the apoptotic activity of EMP in embryonic vasculature was related to a marked reduction in vessel area, vessel diameter and mean capillary area. Based on the qPCR and immunohistochemistry assays, enhanced expression level of BAX and reduced expression level of Bcl-2 confirmed apoptotic responses in the vessels of the YSM. We observed that induction of an apoptotic signal can cause the embryonic defect of the vascular system following EMP treatment. The acquired data also raised suspicions that alteration in apoptotic genes and proteins in the vasculature are two critical pathways in vascular-toxicity of EMP.

16.
Curr Pharm Biotechnol ; 22(9): 1149-1155, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33038909

RESUMO

On a worldwide scale, the outbreak of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has led to extensive damage to the health system as well as the global economy. Hitherto, there has been no approved drug or vaccine for this disease. Therefore, the use of general antiviral drugs is at the first line of treatment, though complicated with limited effectiveness and systemic side effects. Given the pathophysiology of the disease, researchers have proposed various strategies not only to find a more specific therapeutic way but also to reduce the side effects. One strategy to accomplish these goals is to use CRISPR/Cas13 system. Recently, a group of scientists has used the CRISPR/Cas13 system, which is highly effective in eliminating the genome of RNA viruses. Due to the RNA nature of the coronavirus genome, it seems that this system can be effective against the disease. The main challenge regarding the application of this system is to deliver it to the target cells efficiently. To solve this challenge, it seems that using virosomes with protein S on their membrane surface can be helpful. Studies have shown that protein S interacts with its specific receptor in target cells named Angiotensin-Converting Enzyme 2 (ACE2). Here, we propose if CRISPR/Cas13 gene constructs reach the infected cells efficiently using a virosomal delivery system, the virus genome will be cleaved and inactivated. Considering the pathophysiology of the disease, an important step to implement this hypothesis is to embed protein S on the membrane surface of virosomes to facilitate the delivery of gene constructs to the target cells.


Assuntos
COVID-19 , SARS-CoV-2 , Antivirais , Sistemas CRISPR-Cas , Genoma Viral , Humanos
17.
Environ Sci Pollut Res Int ; 28(40): 57216-57231, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34086178

RESUMO

Pesticides are potentially hazardous chemicals that can cause injury to human health and the environment. The purpose of this study was to evaluate organophosphate pesticides (OPPs) and organochlorine pesticides (OCPs) exposure in farmworkers' children aged 6 to 11 years in Jiroft city in southeastern Iran. One hundred twenty farmworkers' children as case and 53 non-farmworkers' children aged 6 to 11 years as control were selected and the serum levels of OCPs were measured by using gas chromatography in all participants. In addition, erythrocyte acetylcholinesterase (AChE) and arylesterase activity of paraoxonase-1 (PON-1) were measured to evaluate OPPs effects. Catalase (CAT), superoxide dismutase3 (SOD3), glutathione peroxidase (GPx3) activities, and the levels of serum malondialdehyde (MDA), total antioxidant capacity (TAC), nitric oxide (NO), and protein carbonyl (PC) were measured to investigate OCPs and OPPs effects on oxidative stress (OS). The serum levels of beta-HCH, 4,4 DDE, and 4,4 DDT in the case group were significantly higher than the control group. In addition, in the case group, AChE, PON-1, CAT, SOD3, and GPx3 activities and the levels TAC were significantly lower, while MDA, PC, and NO levels were significantly higher than the control group. OCPs as illegal pesticides are present in southeast Iran and children are exposed to OCPs and OPPs in the studied area. In addition, higher serum levels of pesticides may be a major contributor in OS development, as a cause of many diseases.


Assuntos
Exposição Ambiental/efeitos adversos , Hidrocarbonetos Clorados , Praguicidas , Acetilcolinesterase , Arildialquilfosfatase , Estudos de Casos e Controles , Criança , Fazendeiros , Glutationa Peroxidase , Humanos , Hidrocarbonetos Clorados/efeitos adversos , Irã (Geográfico) , Malondialdeído , Estresse Oxidativo , Praguicidas/efeitos adversos , Superóxido Dismutase
18.
Epigenomics ; 13(24): 1939-1960, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34852637

RESUMO

miRNA-148b belongs to the family miR-148/-152, with significant differences in nonseed sequences, which can target diverse mRNA molecules. Reportedly, it may undergo deregulation in lung and ovarian cancers and downregulation in gastric, pancreatic and colon cancers. However, there is a need for further studies to better characterize its mechanism of action and in different types of cancer. In this review, we focus on the aberrant expression of miR-148b in different cancer types and highlight its main target genes and signaling pathways, as well as its pathophysiologic role and relevance to tumorigenesis in several types of cancer.


Lay abstract miRNA-148b, or miR-148b, is a tumor suppressor that can regulate invasion-, apoptosis- and proliferation-related oncogenes. miR-148b prognostic and diagnostic potential has been the center of focus recent investigations and extensive studies have been performed on miR-148b regulation in carcinogenesis. Here, we review the role of miR-148b in various cancers and its potential therapeutic application as a target or biomarker.


Assuntos
MicroRNAs , Neoplasias , Apoptose/genética , Proliferação de Células , Regulação para Baixo , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias/genética
19.
Pathol Res Pract ; 221: 153443, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33930607

RESUMO

Since the outbreak of the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the control of virus spread has remained challenging given the pitfalls of the current diagnostic tests. Nevertheless, RNA amplification techniques have been the gold standard among other diagnostic methods for monitoring clinical samples for the presence of the virus. In the current paper, we review the shortcomings and strengths of RT-PCR (real-time polymerase chain reaction) techniques for diagnosis of coronavirus disease (COVID)-19. We address the repercussions of false-negative and false-positive rates encountered in the test, summarize approaches to improve the overall sensitivity of this method. We discuss the barriers to the widespread use of the RT-PCR test, and some technical advances, such as RT-LAMP (reverse-transcriptase-loop mediated isothermal amplification). We also address how other molecular techniques, such as immunodiagnostic tests can be used to avoid incorrect interpretation of RT-PCR tests.


Assuntos
Teste para COVID-19/métodos , COVID-19/diagnóstico , Reação em Cadeia da Polimerase em Tempo Real/métodos , SARS-CoV-2/isolamento & purificação , Humanos
20.
Front Oncol ; 11: 650256, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33987085

RESUMO

Digestive system cancer tumors are one of the major causes of cancer-related fatalities; the vast majority of them are colorectal or gastric malignancies. Epidemiological evidence confirmed that allium-containing food, such as garlic, reduces the risk of developing malignancies. Among all compounds in garlic, allicin has been most researched, as it contains sulfur and produces many second degradation compounds, such as sulfur dioxide, diallyl sulfide (DAS), diallyl trisulfide (DATS), and diallyl disulfide (DADS) in the presence of enzymatic reactions in gastric juice. These substances have shown anti-inflammatory, antidiabetic, antihypertensive, antifungal, antiviral, antibacterial, and anticancer efficacy, including gastrointestinal (GI) cancers, leukemia, and skin cancers. Herein, we summarize the therapeutic potential of allicin in the treatment of GI cancers.

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