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BACKGROUND AND AIM: Colorectal cancer (CRC) originates from pre-existing polyps in the colon. The development of different subtypes of CRC is influenced by various genetic and epigenetic characteristics. CpG island methylator phenotype (CIMP) is found in about 15-20% of sporadic CRCs and is associated with hypermethylation of certain gene promoters. This study aims to find prognostic genes and compare their expression and methylation status as potential biomarkers in patients with serrated sessile adenomas/polyps (SSAP) and CRC, in order to evaluate which, one is a better predictor of disease. METHOD: This study employed a multi-phase approach to investigate genes associated with CRC and SSAP. Initially, two gene expression datasets were analyzed using R and Limma package to identify differentially expressed genes (DEGs). Venn diagram analysis further refined the selection, revealing four genes from the Weissenberg panel with significant changes. These genes, underwent thorough in silico evaluations. Once confirmed, they proceeded to wet lab experimentation, focusing on expression and methylation status. This comprehensive methodology ensured a robust examination of the genes involved in CRC and SSAP. RESULT: This study identified cancer-specific genes, with 8,351 and 1,769 genes specifically down-regulated in SSAP and CRC tissues, respectively. The down-regulated genes were associated with cell adhesion, negative regulation of cell proliferation, and drug response. Four highly downregulated genes in the Weissenberg panel, including CACNA1G, IGF2, MLH1, and SOCS1. In vitro analysis showed that they are hypermethylated in both SSAP and CRC samples while their expressions decreased only in CRC samples. CONCLUSION: This suggests that the decrease in gene expression could help determine whether a polyp will become cancerous. Using both methylation status and gene expression status of genes in the Weissenberg panel in prognostic tests may lead to better prognoses for patients.
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Neoplasias Colorretais , Ilhas de CpG , Metilação de DNA , Regulação Neoplásica da Expressão Gênica , Fator de Crescimento Insulin-Like II , Proteína 1 Homóloga a MutL , Proteína 1 Supressora da Sinalização de Citocina , Humanos , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Neoplasias Colorretais/metabolismo , Proteína 1 Supressora da Sinalização de Citocina/genética , Proteína 1 Supressora da Sinalização de Citocina/metabolismo , Metilação de DNA/genética , Fator de Crescimento Insulin-Like II/genética , Fator de Crescimento Insulin-Like II/metabolismo , Regulação Neoplásica da Expressão Gênica/genética , Proteína 1 Homóloga a MutL/genética , Proteína 1 Homóloga a MutL/metabolismo , Ilhas de CpG/genética , Feminino , Pólipos do Colo/genética , Pólipos do Colo/metabolismo , Pólipos do Colo/patologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Masculino , Regulação para Baixo/genética , Simulação por Computador , Pessoa de Meia-Idade , Adenoma/genética , Adenoma/metabolismo , Adenoma/patologia , Regiões Promotoras Genéticas/genética , Canais de Cálcio Tipo T/genética , Canais de Cálcio Tipo T/metabolismo , Perfilação da Expressão Gênica/métodos , Idoso , PrognósticoRESUMO
Inflammatory bowel disease (IBD) manifests as chronic inflammation within the gastrointestinal tract. The study focuses on a long noncoding RNA (lncRNA) known as Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1). MALAT1's misregulation has been linked with various autoimmune diseases and regulates proinflammatory cytokines. The role of IL6 in immune-triggered conditions, including IBD, is another focal point. In this research, the expression of MALAT1 and IL6 in IBD patients was meticulously analyzed to uncover potential interactions. The study involved 33 IBD patients (13 with Crohn's disease and 20 with ulcerative colitis) and 20 healthy counterparts. Quantitative real-time polymerase chain reaction determined the MALAT1 and IL6 gene expression levels. The competitive endogenous RNA (ceRNA) regulatory network was constructed using several tools, including LncRRIsearch and Cytoscape. A deep dive into the Inflammatory Bowel Disease database was undertaken to understand IL6's role in IBD. Drugs potentially targeting these genes were also pinpointed using DGIdb. Results indicated a notable elevation in the expression levels of MALAT1 and IL6 in IBD patients versus healthy controls. MALAT1 and IL6 did not show a direct linear correlation, but IL6 could serve as MALAT1's target. Analyses unveiled interactions between MALAT1 and IL6, regulated by hsa-miR-202-3p, hsa-miR-1-3p, and has-miR-9-5p. IL6's pivotal role in IBD-associated inflammation, likely interacting with other cytokines, was accentuated. Moreover, potential drugs like CILOBRADINE for MALAT1 and SILTUXIMAB for IL6 were identified. This research underscored MALAT1 and IL6's potential value as targets in diagnosis and treatment for IBD patients.
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Doenças Inflamatórias Intestinais , MicroRNAs , RNA Longo não Codificante , Humanos , Citocinas , Inflamação/metabolismo , Doenças Inflamatórias Intestinais/genética , Interleucina-6/genética , MicroRNAs/genética , RNA Longo não Codificante/genéticaRESUMO
Ovarian cancer stands as a leading cause of cancer-related deaths among women globally. This malignancy has hindered successful treatment attempts due to its inherent resistance to chemotherapy agents. The utilization of cisplatin and doxorubicin-loaded liposomes emerges as a strategically advantageous approach in the realm of biomedical applications. This strategy holds promise for augmenting drug efficacy, mitigating toxicity, refining pharmacokinetics, and facilitating versatile drug delivery while accommodating combination therapies. In pursuit of scholarly investigations, the eminent databases, including PubMed/MEDLINE, ScienceDirect, Scopus, and Google Scholar, were meticulously scrutinized. Within this study, a nano-liposomal formulation was meticulously designed to serve as a co-delivery system. This system was optimized by varying lipid concentrations, hydration time, and DSPC: cholesterol molar ratios to efficiently encapsulate and load doxorubicin (DOX) and cisplatin (CIS) to overcome drug resistance problems. The Lipo (CIS + DOX) formulation underwent rigorous characterization including dimensions, entrapment efficiencies and drug release kinetics. Notably, the entrapment efficiency of cisplatin and doxorubicin loaded liposomal nanoparticles was an impressive 85.29 ± 1.45 % and 73.62 ± 1.70 %, respectively. Furthermore, Lipo (CIS + DOX) drug release kinetics exhibited pH-dependent properties, with lower drug release rates at physiological pH (7.4) than acidic (pH 5.4). Subsequent cytotoxicity assays revealed the enhanced biocompatibility of dual-drug liposomes with HFF cells compared to free drug combinations. Impressively, CIS and DOX-loaded liposomes induced significant cytotoxicity against A2780 in comparison to free drugs and combinatorial free drugs. Furthermore, the CIS and DOX-loaded liposome showed induced apoptotic potential and cell cycle arrest in A2780 compared to CIS, DOX, and their combination (CIS + DOX). Combining CIS and DOX via liposomal nanoparticles introduces a promising therapeutic avenue for addressing ovarian cancer. These nano-scale carriers hold the potential for attenuating the untoward effects of singular drugs and their attendant toxicities.
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Aim: This study aimed to evaluate the effect of supplementation with ground flaxseed (GF) on the concentrations of adiponectin, resistin, and visfatin in patients with ulcerative colitis (UC). Background: Inflammatory bowel disease (IBD) is one of the most common gastrointestinal diseases affecting people of all ages. Adipokines secreted from adipose tissue have been shown to play an essential role in the pathogenesis of UC. Methods: This trial is an open-labeled randomized controlled trial conducted on 70 patients with UC. The patients were randomly divided into two groups: flaxseed and control. The patients in the intervention received 30 g/day flaxseed powder for 12 weeks. Patients' anthropometric, nutritional, and biochemical factors were evaluated at the beginning and end of the intervention period. Results: Totally, 64 patients (36 men and 28 women) with a mean age of 31.12±9.67 were included in the final analysis. There was no significant difference between the two groups regarding baseline weight and height (P>0.05). After the 12-week intervention, flaxseed supplementation led to a significant reduction in the resistin (-4.85±1.89 vs. -1.10±2.25, P<0.001) and visfatin concentration (-1.33±1.14 vs. -0.53±1.63, P=0.018). Further, we found a significant increase in the adiponectin levels after the GF supplementation (3.49±1.29 vs. -0.35±0.96, P<0.001). Conclusion: Flaxseed supplementation could exert beneficial effects on adipokine levels in patients with UC.
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Background: Ulcerative colitis (UC) and Crohn's disease (CD) are two major types of inflammatory bowel diseases (IBDs). Toll-like receptors (TLRs) are expressed in the innate immune system compartments, in charge of identifying a wide range of microorganisms. The aim of the present study was to evaluate the expression of TLR-2, -7, and -8 in peripheral blood mononuclear cells (PBMC) of UC patients as a novel non-invasive primary inflammation sensor for monitoring the clinical course of UC candidates. Materials and Methods: In this cross-sectional study, total RNA was extracted from the PBMC of 42 UC patients along with 20 healthy donors. The mRNA levels of TLR-2, -7, and -8 were assessed using the quantitative real-time polymerase chain (qRT-PCR) reaction. Results: The present research study demonstrated no significant changes in TLR-2 mRNA expression in UC patients in comparison with the control group (P = 0.1264), whereas significant elevation (P = 0.0008) was distinguished in the TLR-7 expression of UC participants specifically during the remission course compared with healthy donors and flareup patients (P = 0.0004 and P = 0.0063, respectively). The last selected TLR, TLR-8 was not shown remarkable changes either between UC patients and the control group or between clinical courses of the disease. Conclusion: Here, among three nominated TLRs for predicting UC patients, TLR-7 was potentially selected according to the significant difference in mRNA expression in flareup UC patients and control donors. TLR-7 could be used as a novel non-invasive biomarker for monitoring UC patients in the active course of the disease.
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CDKN1A gene is implicated in cell differentiation, development process, repair, apoptosis, senescence, migration, and tumorigenesis. Somatic alterations and polymorphisms may interfere in the function of CDKN1A, and this could affect the individual susceptibility to colorectal cancer (CRC). Here in, we evaluated the importance of single nucleotide polymorphic variants in codon 31 of CDKN1A (rs1801270: C > A) for the development of colorectal cancer in an Iranian population. A total of 150 CRC patients and 150 healthy controls were enrolled in this study. Genomic DNA was extracted from peripheral blood specimens. Genotypes were determined using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) assay. In CRC patients, the genotype frequencies detected were 90%, 8.0% and 2.0%2 for CC, AC and AA genotypes while the genotype frequencies in control group were 78%, 20.7% and 1.35% 1.35% for CC, AC and AA genotype, respectively. There were statistically significant differences in the distribution of CDKN1A rs1801270 genotypes and allele frequencies between colorectal cancer patients and healthy controls (p value = 0.021). Also, results indicated a significant negative association between AC genotype and risk of colorectal cancer occurrence. (Odds ratio (OR)=0.357; 95% confidence interval (CI)=0.168-0.760, p = 0.007). Our data suggest that the AC genotype may have a protective role in the development of CRC in an Iranian population.
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Neoplasias Colorretais , Predisposição Genética para Doença , Humanos , Irã (Geográfico)/epidemiologia , Polimorfismo de Nucleotídeo Único , Neoplasias Colorretais/genética , Genótipo , Inibidor de Quinase Dependente de Ciclina p21RESUMO
Gastrointestinal (GI) cancers comprise a significant number of cancer cases worldwide and contribute to a high percentage of cancer-related deaths. To improve survival rates of GI cancer patients, it is important to find and implement more effective therapeutic strategies with better prognoses and fewer side effects. The development of new drugs can be a lengthy and expensive process, often involving clinical trials that may fail in the early stages. One strategy to address these challenges is drug repurposing (DR). Drug repurposing is a developmental strategy that involves using existing drugs approved for other diseases and leveraging their safety and pharmacological data to explore their potential use in treating different diseases. In this paper, we outline the existing therapeutic strategies and challenges associated with GI cancers and explore DR as a promising alternative approach. We have presented an extensive review of different DR methodologies, research efforts and examples of repurposed drugs within various GI cancer types, such as colorectal, pancreatic and liver cancers. Our aim is to provide a comprehensive overview of employing the DR approach in GI cancers to inform future research endeavors and clinical trials in this field.
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BACKGROUND: Celiac disease (CeD) and inflammatory bowel disease (IBD) are accompanied by impaired immune responses. To study the immune regulation of these diseases, we evaluated the expression levels of pro-inflammatory (IL-8 and IL-17 A) and anti-inflammatory (IL-10) cytokines in intestinal biopsy specimens of CeD and IBD patients in comparison to healthy subjects. METHODS AND RESULTS: Intestinal biopsies were collected from 33 patients with IBD, 47 patients with CeD, and 20 healthy individuals. Total RNA was extracted and mRNA expression levels of IL-8, IL-17 A and IL-10 were assessed by qPCR. P-value < 0.05 was considered statistically significant. The expression levels of IL-8 and IL-17 A were higher in biopsies of IBD (UC and CD) and CeD patients compared to the control group (P < 0.05). IBD patients (UC and CD) had higher IL-8 intestinal level than CeD patients (P < 0.0001 and P = 0.0007, respectively). The expression of IL-10 was significantly down-regulated in intestinal biopsies of CeD and IBD patients compared with controls (P < 0.001). In addition, the expression level of this cytokine was significantly lower in IBD patients (P < 0.001 for UC patients and P < 0.0001 for CD patients) than CeD group. CONCLUSIONS: The three selected pro- and anti-inflammatory cytokines showed a similar expression pattern in both IBD and CeD patients. As IBD and CeD are immune-mediated disorders and are accompanied by inflammatory events, the understanding of the similarities and differences among them can help researchers to find out useful candidate therapeutic protocols. We suggest that larger cohort studies be organized to achieve more insights into this regulation.
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Colite Ulcerativa , Doenças Inflamatórias Intestinais , Colite Ulcerativa/genética , Citocinas/metabolismo , Expressão Gênica , Humanos , Doenças Inflamatórias Intestinais/genética , Interleucina-10/genética , Interleucina-17/genética , Interleucina-17/metabolismo , Interleucina-8/genética , Mucosa Intestinal/metabolismoRESUMO
The growth of pancreatic cancer has a high predominance in the world. Different therapeutic methods were unsuccessful due to tumor invasion and rapid metastasis. Plants have natural products that were used as therapeutic agents. Accordingly, the purpose of this research was to assess the cytotoxic effect of Portulaca Oleracea against PANC-1 cancer cell line. MTT technique and flow cytometry were done to evaluate the cytotoxicity of P.Oleracea extracts against PANC-1 cancer cell line. For finding the change of CDK and P53 expression levels, qPCR carries out. The findings of the MTT assay exhibited that P.Oleracea extracts had toxicity potential on PANC- one cancer cell line. Also, the results of gene expression showed the high expression of P53 and reduction of CDK gene expression following treatment of cancer cells with plant extracts in. The flow cytometry assay showed apoptosis induced after P.Oleracea extract treatment in PANC- one cancer cell line. Also, microscopic observation is in agreement with flow cytometry and MTT assay. Results of the current study indicated that P.Oleracea extracts significantly induce apoptosis by regulating P53 and CDK expression, consequently. Therefore, P.Oleracea may be considered as a novel finding for pancreatic cancer treatment consequently of its cytotoxic and apoptotic activity.
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Antineoplásicos , Neoplasias Pancreáticas , Portulaca , Antineoplásicos/farmacologia , Apoptose , Proteína Quinase CDC2/farmacologia , Linhagem Celular , Expressão Gênica , Humanos , Neoplasias Pancreáticas/tratamento farmacológico , Extratos Vegetais/farmacologia , Proteína Supressora de Tumor p53/genética , Neoplasias PancreáticasRESUMO
The pathogenesis of inflammatory bowel disease (IBD) is influenced by immune system malfunction, particularly innate immune receptors such as toll-like receptors. Furthermore, it is critical to investigate the extremely close association between viruses and IBD incidence. Toll-like receptors (TLRs) 3, 5, and 7 are involved in antiviral immune responses. Finding a relationship between TLR-related virus and IBD is important not only for understanding the disease pathogenesis, but also for developing effective therapies. It has been shown that influenza is expressed more severely in patients with IBD who use immune system inhibitors, and the influenza vaccine is less effective in these patients. In dendritic cells, TLR7 and TLR8 regulate the production of interferons (IFNs) and inflammatory mediators. COVID-19 causes the production of IL-6, possibly due to the induction of TLR pathways. TLR activation by SARS-CoV-2 causes inflammation and IL-1 production, which induces the production of IL-6. Understanding TLR-associated viruses' molecular mechanisms can greatly help improve the quality of life of people with IBD. Therefore, the present study reviewed the role of TLR7, 8, and 3 in inflammatory bowel disease as well as their association with viral infections and evaluated different antagonists for the treatment of IBD.
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AIM: The aim of this study was to evaluate the expression of MALAT1 and the relationship between its expression with clinical characteristics in an Iranian gastric cancer patient. BACKGROUND: Long non-coding RNAs (LncRNAs) play critical roles in the initiation and development of gastric cancer. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a highly conserved lncRNA and plays key roles in various types of human cancer. However, our understanding of the role of lncRNAs in the occurrence and development of gastric cancer is not fully clear. METHODS: This cross-sectional study was performed on 41 gastric tumor tissue samples with matched normal adjacent tumor tissues. The RNA level of lncRNA MALAT1 gene was assessed using quantitative Real-time polymerase chain reaction. B2M was used as an internal control. The 2 -ΔΔCq method was adopted to determine expression fold changes. RESULTS: A significant association was observed between the levels of MALAT1 in gastric tumor tissues compared with normal adjacent tissues (mean= 1.558, p= 0.014). In addition, clinicopathologic data on MALAT1 RNA expression levels in gastric cancer tissues was evaluated. No significant association was observed between the relative expression of MALAT1 and the stage, grade, H. pylori infection, and tumor size groups among gastric cancer patients (p= 0.82, p= 0.904, p= 0.407, and p= 0.701, respectively). CONCLUSION: The current results showed that MALAT1 has a significant association in gastric cancer. The expression of MALAT1 may be used as a diagnostic biomarker for monitoring gastric cancer patients.
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AIMS: Inflammatory bowel disease, a chronic inflammatory disorder of the intestinal mucosa, is a clinical presentation of Crohn's disease and ulcerative colitis (UC). This study investigated the effect of grounded flaxseed (GF) and flaxseed oil (FO) on clinical biomarkers, quality of life and diseases activity in patients with UC. This research was conducted among 90 patients with UC for 12 weeks using an open-labelled randomised controlled trial design. METHODS: The participants were randomly assigned into two intervention groups supplemented with GF (30 gr/day) and FO (10 gr/day) as well as a control group. The participants' data were collected prior to and 12 weeks after the intervention. The one-way analysis of variance was run to compare variables. RESULTS: A total of 75 patients completed the study. After the intervention, hs-CRP (P < .001) and Mayo score (P < .001) were reduced significantly, but quality of life was increased significantly (P < .001) in the GF and FO groups compared with the control. A significant increase was observed in IL-10 concentration in the FO group, but no significant change was found in serum levels of IL-10 in the control group. Moreover, the decrease in Mayo score was greater in patients at more severe stages of the disease (P < .05). No difference was observed between the intervention groups and control group in mRNA expression level of TLR4 at the 12th week. CONCLUSION: In conclusion, grounded flaxseed and FO attenuated systemic inflammation and improved disease severity in UC patients.
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Colite Ulcerativa , Linho , Colite Ulcerativa/tratamento farmacológico , Suplementos Nutricionais , Expressão Gênica , Humanos , Inflamação , Qualidade de VidaRESUMO
Background and Aims: Interleukin-15 (IL-15) is a key player in the pathogenesis of celiac disease (CD). We investigated the functional role of IL-15 in the process of epithelial cell phenotypic modification at different stages of CD. Materials and Methods: In this study, we looked for correlations between the IL-15 mRNA levels in duodenal tissue and serum protein levels in a cohort of Iranian patients affected by CD based on the degree of histopathology. Ninety-five formalin-fixed, paraffin-embedded duodenal tissue specimens were collected: 23 with a Marsh I value; 30 with a Marsh II value; 32 with a Marsh III value; and 10 normal controls. The expression levels of the IL-15 gene in these biopsy specimens were determined by real-time quantitative polymerase chain reaction (qPCR), and IL-15 serum protein concentrations were determined by enzyme-linked immunosorbent assay and compared to tissue expression. Results: The IL-15 mRNA levels were higher in patients with Marsh II compared with the control group, and the Marsh I, and Marsh III groups. The differences between the Marsh II and Marsh I patients were statistically significant (p = 0.03). Similarly, the serum concentration of IL-15 was higher in Marsh II patients compared to those with Marsh I and Marsh III lesions, although the differences were not statistically significant (p = 0.221). Conclusions: Our results demonstrate that IL-15 gene expression might be elevated only in the early stages of CD onset (and histological damage) and that IL-15 serum levels do not significantly correlate with its tissue expression whatever the degree of histopathology.
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Doença Celíaca/genética , Interleucina-15/genética , Adolescente , Adulto , Idoso , Atrofia/patologia , Biópsia , Doença Celíaca/sangue , Duodeno/metabolismo , Duodeno/patologia , Duodeno/fisiologia , Ensaio de Imunoadsorção Enzimática , Feminino , Expressão Gênica/genética , Humanos , Interleucina-15/sangue , Irã (Geográfico) , Masculino , Pessoa de Meia-Idade , Transcriptoma/genéticaRESUMO
Colorectal cancer (CRC) is a common intestinal cancer with a high mortality rate. Early detection of this type of cancer is fundamental to the prevention of the disease, which results in improved survival rates. In the human colon tissue, transition from normal epithelium to adenoma is considered to be caused by unknown molecular incidents occurring over 5-10 years. The detection of CRC has proved problematic when in the early stages of disease. In addition, identifying suitable biomarkers for the detection of CRC progress in patients remains one of the most significant challenges. Long non-coding RNAs have been demonstrated to contribute to the promotion of CRC. The aim of the present study was to investigate the clinical and biological significance of long intergenic non-coding (linc)RNA-p21, lincRNA-regulator of reprogramming (ROR) and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in the colon tumor and polyp tissue, and the association that these have with the expression of p53 at the mRNA level. Neoplastic and paired adjacent normal tissue samples were obtained from 72 patients (46 polyps and 26 tumors). Reverse transcription-quantitative PCR was performed to determine the relative fold changes in the expression of lincRNA-p21, lincRNA-RoR, MALAT1 and p53 in the samples. A significant association was observed between the levels of MALAT1 and p53 in neoplasm tissues (R=0.073; P<0.05). The relative expression of the MALAT1 gene revealed a statistically significant difference between the different polyp types and number of polyps (P=0.0028 and 0.022, respectively). Adjuvant therapy in patients with tumors revealed an association between the levels of lincRNA-ROR and lincRNA-p21 expression (P=0.015 and 0.038, respectively). MALAT1 may be selected as an early detection biomarker for CRC. Furthermore, lincRNA-ROR and lincRNA-p21 may serve as prognostic and therapeutic biomarkers in patients with CRC.
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OBJECTIVE: The present study aimed to evaluate the possible effect of grounded flaxseed and flaxseed oil on serum levels of inflammatory markers, metabolic parameters, and the severity of disease in patients with UC. METHODS: In this open-labeled randomized controlled trial, 90 UC patients were randomly assigned to one of the 3 groups for 12 weeks: grounded flaxseed (GF; 30â¯g/day), flaxseed oil (FO; 10â¯g/day) and control group. The weight, waist circumference, systolic and diastolic blood pressure, serum inflammatory markers (interleukin-6 (IL-6), interferon gamma (INF-γ), transforming growth factor beta (TGF-ß), and Erythrocyte Sedimentation Rate (ESR)), and fecal calprotectin were measured at the baseline and end of the study. RESULTS: Totally, 75 patients (43 men and 32 women) with a mean age of 31.54⯱â¯9.84 years participated in the present study. Comparing the change of the variables indicated a significant decrease in fecal calprotectin (Pâ¯<â¯0.001), Mayo score (Pâ¯<â¯0.001), ESR (Pâ¯<â¯0.001), INF-γ (Pâ¯<â¯0.001), IL-6 (Pâ¯<â¯0.001), waist circumference (Pâ¯=â¯0.02), Diastolic Blood Pressure (DBP) (Pâ¯<â¯0.001), and Systolic Blood Pressure (SBP) (Pâ¯<â¯0.001) and a significant increase in TGF-ß (Pâ¯<â¯0.001) and Inflammatory Bowel Disease Questionnaire-Short form (IBDQ-9) score (Pâ¯<â¯0.001) in the GF and FO groups compared to the control. No difference was obvious between the FO and GF groups except for TGF-ß. CONCLUSION: The present study showed that both flaxseed and flaxseed oil, attenuate inflammatory markers, disease severity, blood pressure, and WC. However, the effect of flaxseed on weight and BMI was not evident.
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Biomarcadores/sangue , Colite Ulcerativa/tratamento farmacológico , Linho/química , Mediadores da Inflamação/sangue , Inflamação/sangue , Óleo de Semente do Linho/uso terapêutico , Adulto , Pressão Sanguínea/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Colite Ulcerativa/sangue , Suplementos Nutricionais , Feminino , Humanos , Óleo de Semente do Linho/farmacologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Índice de Gravidade de Doença , Circunferência da Cintura/efeitos dos fármacosRESUMO
Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide, representing 13% of all cancers. The role of epigenetics in cancer diagnosis and prognosis is well established. MicroRNAs in particular influence numerous cancer associated processes including apoptosis, proliferation, differentiation, cell-cycle controls, migration/invasion and metabolism. MiRNAs-137 and 342 are exon- and intron-embedded, respectively, acting as tumour-suppressive microRNA via hypermethylation events. Levels of miRNAs 137 and 342 have been investigated here as potential prognostic markers for colorectal cancer patients. The methylation status of miRNA-137 and miRNA-342 was evaluated using methylation-specific (MSP) polymerase chain reaction (PCR) on freshly frozen tissue derived from 51 polyps, 8 tumours and 14 normal colon mucosa specimens. Methylation status of miRNA-137 and miRNA-342 was significantly higher in tumour lesions compared to normal adjacent mucosa. Surprisingly, the methylation frequency of miR-342 (76.3%) among colorectal cancer patients was significantly higher compared to miR-137 (18.6%). Furthermore, normal tissues, adjacent to the lesions (N-Cs), displayed no observable methylation for miRNA-137, whereas 27.2% of these N-Cs showed miRNA-342 hypermethylation. MiRNA-137 hypermethylation was significantly higher in male patients and miR-342 hypermethylation correlated with patient age. Methylation status of miRNA-137 and miRNA-342 has both diagnostic and prognostic value in CRC prediction and prevention.
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Neoplasias Colorretais/genética , Metilação de DNA , MicroRNAs/genética , Adolescente , Adulto , Fatores Etários , Biomarcadores Tumorais/genética , Neoplasias Colorretais/diagnóstico , Ilhas de CpG , Epigênese Genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Regiões Promotoras Genéticas , Fatores Sexuais , Adulto JovemRESUMO
Background The aim of the current study was to evaluate the efficacy of D-penicillamine in the treatment of lead poisoning mainly in the outpatient setting. Methods In a case series study performed during the recent epidemic of lead poisoning in Iran, lead-poisoned patients referring to our outpatient clinic were treated with 250-mg D-penicillamine capsules administered every 6 h for 5 or 10 days based on availability of the medication. They were recommended to re-check blood lead level (BLL) 4 weeks after cessation of the treatment and refer to our clinic again. Results In 63 patients with lead poisoning but without signs and symptoms of lead encephalopathy, median BLL was 106 [84, 131] µg/dL on presentation, which declined to a mean of 52.6 ± 28.8 µg/dL after a median treatment period of 7 [5, 10] days (p < 0.001). There was no statistically significant difference between the 5- and 10-day treatment protocols regarding complications and recovery. Treatment had resulted in a median decrease of 54 µg/dL [33, 90] (range: -20 to 231 µg/dL) in the patients' BLLs (33.9% declined in BLL measurements; range: -29.69% to 99.06%). Conclusions D-penicillamine may be an acceptable substitute treatment in adult lead poisoning. Although our sample size was limited, we could not detect any serious adverse effects in our cases showing that D-penicillamine resulted in acceptable recovery rates. This may be helpful especially in epidemics with limitations in antidote access.
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Antídotos/uso terapêutico , Intoxicação por Chumbo/tratamento farmacológico , Penicilamina/uso terapêutico , Administração Oral , Adulto , Antídotos/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Humanos , Irã (Geográfico) , Intoxicação por Chumbo/epidemiologia , Masculino , Pessoa de Meia-Idade , Penicilamina/administração & dosagemRESUMO
BACKGROUND: Inflammatory bowel disease (IBD) is one of the most important immune-mediated disorders of the gastrointestinal tract. Besides, IBD is associated with numerous extraintestinal complications such as venous thromboembolism (VTE), an important risk factor for vascular complications, which results in the increased morbidity and mortality. The JAK2 (Janus kinase 2) V617F mutation is a well-known point mutation which is involved in the pathogenesis of IBD, and VTE. Therefore, the aims of this study were to evaluate expression of JAK2 and association of V617F mutation in JAK2 of Iranian patients with IBD. METHODS: Two hundred and forty-six patients with IBD (209 UC and 37 CD) and 206 healthy controls were enrolled in this study. The genomic DNA and total RNA were extracted from peripheral blood mononuclear cells (PBMCs). Then, the JAK2 V617F mutation detection was performed using the restriction fragment length polymorphism (RFLP) method. In addition, the JAK2 mRNA expression was evaluated using a quantitative polymerase chain reaction (q-PCR) using the SYBR Green assay. RESULTS: There was no association of V61F mutation in patients with IBD with or without thrombosis compared with healthy control. However, the relative mRNA expression of JAK2 was significantly upregulated in patients with IBD in comparison with healthy control (P < 0.0001). In addition, the JAK2 mRNA expression was significantly decreased in patients with IBD having thrombosis compared with those without thrombosis ( P < 0.0001). CONCLUSIONS: Taken together our findings suggested that JAK2 V61F-independent upregulation of JAK2 mRNA expression in patients with IBD. Moreover, despite the absence of JAK2 V617F mutation in patients with IBD, the increased gene expression of JAK2 can be explained by another molecular mechanism such as regulation of gene expression at the transcriptional level which may play crucial roles in the pathogenesis of IBD.
Assuntos
Doenças Inflamatórias Intestinais/genética , Janus Quinase 2/genética , Mutação Puntual , Regulação para Cima , Adulto , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Humanos , Irã (Geográfico) , Leucócitos Mononucleares/química , MasculinoRESUMO
AIM: This study set out to determine the effect of methylation on MALAT1 gene in primary colorectal lesions and tumors to gain further knowledge about the diagnostic and prognostic value of MALAT. BACKGROUND: Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is one of the long non-coding RNAs that plays an important role in invasion, cell proliferation, and metastasis of various cancers. However, there is insufficient information on the association between MALAT1 and the methylation process as well as its role in the development of colorectal cancer. METHODS: Methylation pattern of MALAT1 promoter was determined by Methylation-Specific Polymerase Chain Reaction (MSP) in 86 colorectal primary lesions, tumors, and normal specimens. MALAT1 methylation pattern was compared in tumor and polyp tissue. In order to obtain more accurate results, we investigated the association between MALAT1 promoter methylation pattern and clinicopathologic factors in patients. RESULTS: The results indicated that the MALAT1 promoter methylation pattern in the tumor tissue, primary lesion tissue, and normal was not significantly different (p=0.430). Comparison of the MALAT1 promoter methylation pattern between polyp types and tumor tissue groups was not significant either (p=0.437). Surprisingly, the methylation frequency of MALAT1 methylation was significantly higher in colon lesions than in their rectum lesion (p = 0.035). In addition, no significant hypermethylation of MALAT1 was observed between the other patients' clinicopathological data in both polyp 46/66 and tumor tissues 20/66. CONCLUSION: This study dealt with determining the effect of methylation on MALAT1 gene in primary colorectal lesions and tumors to gain further knowledge about the diagnostic and prognostic value of MALAT.