EMT is the process by which a polarized epithelial cell undergoes several changes leading to highly invasive and fibroblast-like morphology. It has been described that miR-375 is inversely associated ...with EMT in cancerous patients and can effectively inhibit invasion and migration of tumor cells. Here, we investigate whether miR-375 mimic delivered by tumor-derived exosomes could reverse EMT process.
The exosomes were isolated from HT-29 and SW480. Subsequently, exosomes were loaded with miR-375-3p mimic applying modified calcium chloride method. Quantitative real-time PCR was used for evaluation of the loading efficiency of miR-375 mimic in the exosomes. The effects of miR-375 loaded tumor exosomes (TEXomiR) on EMT process investigated using flow cytometry, cell morphology, and invasion and migration assay.
The in vitro results showed that the tumor derived exosomes can efficiently deliver miR-375 mimic to reduce the expression of β-catenin, vimentin, ZEB1, and snail. In contrast, TEXomiR significantly increased the expression of E- cadherin in EMT process. Furthermore, the migration and invasion abilities of HT-29 and SW480 cells were inhibited by TEXomiR. The expression of CD44 and CD133 are increased in EMT process. Flow cytometry evaluation demonstrated that treatment with TEXomiR significantly decreased the expression of CD44 and CD133 in SW480 cell line.
Our results imply that colon cancer cells-derived exosomes could be used as an effective nonvehicle to deliver miR-375-3p mimic. Moreover, TEXomiR may be a potent therapeutic agent for the treatment of metastatic colorectal cancer.
Colon cancer (CRC) is a heterogeneous disorder, arising from precursors-adenoma and serrated polyp. Previous studies have demonstrated the relationship between the human gut microbiota and CRC; ...however, its correlation to the different early precursors of CRC is not properly understood. Here, we studied the relationship between targeted gut bacteria and different colorectal polyp types, location, size and grade of dysplasia.
In the present case-control descriptive study, selected fecal bacteria were assessed in 118 patients, referred for standard screening colonoscopy, including 31 normal controls, 21 hyperplastic polyp (HP), 16 sessile serrated polyp (SSA), 29 tubular adenoma (TA) and 21 villous/tubuvillous polyp (VP/TVP) cases, between 2015 and 2017, by absolute quantitative real time PCR technique (q PCR) in different ethnicity of Iranian population. The panel of bacteria was including Streptococcus bovis/gallolyticus, Enterococcus faecalis, Enterotoxigenic Bacteroides fragilis (ETBF), Fusobacterium nucleatum, Porphyromonas spp., Lactobacillus spp., Roseburia spp., and Bifidobacterium spp.
Higher numbers of F. nucleatum, E. feacalis, S. bovis, ETBF and Porphyromonas spp. were detected in AP cases, consisting TA and especially VP/TVP, in contrast to samples from the normal, HP and SSA groups (P < 0.001). On the contrary, lower number of Lactobacillus spp., Roseburia spp. and Bifidobacterium spp. were detected in AP, compared to the normal, HP and SSA. Surprisingly, a significant correlation was found among selected gut bacterial quantity, the size, location and grade of dysplasia of polyp cases.
These findings suggest that gut bacteria might contribute in early stages of colorectal carcinogenesis through the development of AP, but not SSA. In fact, AP and SSA are also different in terms of molecular pathways and tendencies to present in specific colorectal location. Overall, these findings may lead to development of CRC prevention therapies, targeting early protagonist bacteria of colorectal carcinogenesis from AP.
Background
Microsatellite instability (MSI) is a prognostic marker in colorectal cancer (CRC). The biological significance of MSI‐low (MSI‐L) phenotype and its differences with microsatellite stable ...(MSS) phenotype remains unclear. The aim of this study is indicating the role of mononucleotide repeat in identifying MSI‐L and revealing the association of MSI‐L with elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) and oncologic outcome in CRC patients.
Methods
MSI and EMAST status were analyzed using three quasimonomorphic panel (BAT‐25, BAT‐26, and NR‐27) and five tetranucleotide repeats (D20S82, D20S85, D9S242, D8S321, and MYCL1), respectively, by capillary electrophoresis method without the need to fluorescent primers. The associations of MSI status with clinicopathological features, EMAST status, metastasis, and overall survival (OS) were investigated.
Results
Among 159 CRC patient 22.0% were MSI‐H, 40.3% were MSS, 37.7% were MSI‐L, and 41.5% showed EMAST + phenotype. MSI‐L were associated with advanced stages, EMAST+ tumors and worse OS (
p ≤ 0.001). Metastasis was relatively common in MSI‐L/EMAST
+ CRCs and BAT‐25 were the most unstable marker in these tumors.
Conclusions
MSI‐L tumors have different clinicopathological features from MSS and MSI‐H tumors. The MSI‐L phenotype is a worse prognostic biomarker in CRC and when accompanied by EMAST could be a predictor for metastasis.
This study evaluated the association of microsatellite instability‐low (MSI‐L) with elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) and oncologic outcome in colorectal cancer (CRC) patients. MSI and EMAST status were analyzed using three mononucleotide repeat and five tetranucleotide repeats panel, respectively. MSI‐L phenotype is a worse prognostic biomarker in CRC and when accompanied by EMAST could be a predictor for metastasis.
Hydatidosis is a disease caused by the larval stage of Echinococcus granulosus, which involves several organs of intermediate hosts. Evidence suggests a communication between hydatid cyst (HC) and ...hosts via extracellular vesicles. However, a little is known about the communication between EVs derived from HC fluid (HCF) and host cells. In the current study, EVs were isolated using differential centrifugation from sheep HCF and characterized by western blot, electron microscope and size distribution analysis. The uptake of EVs by human monocyte cell line (THP‐1) was evaluated. The effects of EVs on the expression levels of pro‐ and anti‐inflammatory cytokines were investigated using quantitative real‐time PCR (RT‐PCR), 3 and 24 h after incubation. Moreover, the cytokine level of IL‐10 was evaluated in supernatant of THP‐1 cell line at 3 and 24 h. EVs were successfully isolated and showed spherical shape with size distribution at 130.6 nm. After 3 h, the expression levels of pro‐inflammatory cytokine genes (IL1Β, IL15 and IL8) were upregulated, while after 24 h, the expression levels of pro‐inflammatory cytokines were decreased and IL13 gene expression showed upregulation. A statistically significant increase was seen in the levels of IL‐10 after 24 h. The main mechanism of the communication between EVs derived from HCF and their host remains unclear; however, time‐dependent anti‐inflammatory effects in our study suggest that HC may modulate the immune responses via EVs.
Diet and lifestyle may affect risk for metabolic-associated fatty liver disease (MAFLD) by chronically elevating systemic inflammation.
In this study we investigated the separate and joint ...associations of dietary and lifestyle inflammation scores (DIS and LIS, respectively) with MAFLD risk.
For this nested case-control study we identified and recruited 968 patients with MAFLD (defined as having a fatty liver index ≥60 plus ≥1 of the following conditions: overweight or obese, type II diabetes mellitus, evidence of metabolic dysregulation) and 964 controls from among 35–70-y-old men and women in the baseline phase of the Sabzevar Persian Cohort Study. We collected demographic, lifestyle, anthropometric, biochemical, and dietary intake information (via a validated FFQ) from which we calculated a circulating inflammation biomarker–weighted, predominantly whole foods and beverages–based, 19-component DIS and a 3-component LIS. We estimated DIS- and LIS-MAFLD associations using multivariable unconditional logistic regression. We also calculated equal-weight DIS and LIS to capture all potential mechanisms (inflammation plus other mechanisms) for associations of diet and lifestyle with MAFLD risk.
Among those in the highest relative to the lowest DIS and LIS tertiles, the multivariable-adjusted ORs and their 95% CIs were OR: 1.84; 95% CI: 1.61, 2.07; Ptrend < 0.001, and OR: 1.96; 95% CI: 1.69, 2.21; Ptrend < 0.001, respectively. For those in the highest relative to the lowest joint DIS and LIS tertile, the values were OR: 2.56; 95% CI: 2.19, 2.93; Pinteraction < 0.001. The findings were similar by sex. The third tertile values for the equal-weight DIS- and LIS-MAFLD associations were OR: 1.87; 95% CI: 1.41, 2.34; and OR: 2.16; 95% CI: 1.85, 2.46, respectively.
Our results suggest that higher balances of pro- relative to anti-inflammatory dietary and lifestyle exposures, separately and especially jointly, may be associated with higher MAFLD risk among adults. Also, inflammation may be the primary mechanism through which diet affects MAFLD risk.
Pancreatic cancer (PC) is one of the most fatal malignancies, and its incidence and mortality rates are growing annually throughout the world. In this research, we aimed to investigate the time ...trends and identify the spatial clusters of incidence and mortality on a global scale over the last 30 years, using the Global Burden of Disease (GBD) study 2019 data.
Age-standardized incidence and mortality data due to PC were extracted from the GBD study, which was carried out from 1990 to 2019. A Joinpoint regression analysis was utilized to examine trends in the incidence and mortality of PC over the past three decades. As such, spatial analyses were undertaken to detect the spatial distribution and clustering of the metrics globally.
It was observed that both the incidence and mortality rates were higher in males than in females worldwide. The global mortality and incidence rates significantly increased by 0.8% per year over the time of follow-up period (p<0.05). By spatial cluster analysis for mortality, European and North African countries, as well as Greenland were explored as hot spots; while South African and Southeast Asian countries were explored as cold spots. Regarding incidence, hot spots were found in European countries, Southern America, and Greenland; whilst cold spots were determined in Southern Africa and Madagascar.
Collectively, the temporal trends disclosed a gradual rise in PC incidence and mortality rates over the period 1990-2019, reflecting the global health concern. We further found geographical variations in the patterns and identified high- and low-risk areas for incidence and mortality. These findings facilitate the design and implementation of more resource-efficient and geographically targeted treatments. Given the results of the current study, a practical approach to minimizing the future PC burden involves planned population-wide interventions, as well as primary prevention through healthier lifestyles.
Natural dietary ingredients like flavonoids are important for body improvement against diseases. The flavonol rutin is widely found in fruits and vegetables and shows significant anticancer ...properties. However, the underlined signaling pathways have not been elucidated yet. In this study, the impacts of various doses of rutin (400–700 mM/ml) have been examined on human colon cancer SW480 cells metabolism, cell cycle, and apoptosis. The transcriptome was analyzed by bioinformatics tools and the interactions between rutin modulated microRNAs (miRNAs), long noncoding RNAs (lncRNAs), messenger RNAs (mRNAs), and transcription factors (TFs) were built, filtered and enriched. A dose of 600 mM of rutin significantly decreased cells metabolic activity, halved the population and arrested the cell cycle at the sub‐G1 phase. The enrichment analysis of miRNAs‐lncRNAs‐mRNAs‐TFs network showed that these effects were mediated through alteration of glucose, lipid, and protein metabolism, modulating endoplasmic reticulum stress responses, negative regulation of cell cycle process, and inducing the extrinsic and intrinsic apoptotic signaling pathways. Additionally, the key parent nodes of each annotation were illustrated. These findings create a detailed image of rutin underlying intracellular signaling pathways in CRC and also help us to better understand the role of dietary natural compounds in cancer treatment.
Treating with the flavonol glycosides rutin suppressed cell cycle and proliferation in human SW480 CRC cells. Analyzing of miRNAs‐lncRNAs‐mRNAs‐TFs interactions showed that these effects have been mediated by impairing cancer cell metabolism, endoplasmic reticulum (ER) stress, cell cycle arrestment at sub‐G0/G1 phase, and extrinsic and intrinsic apoptotic mechanisms.
This study appraises the psychometrics properties of the Inflammatory bowel disease-fatigue (IBD-F) Persian version questionnaire.
The original IBD-F questionnaire was translated into the Persian ...version in a standard forward-back manner. The validation was performed through the face, content, and construct validity. Fifteen experts scored each item's necessity on an ordinal Likert scale of three; then, the content validity ratio was calculated using the Lawshe formula. Eight judges from pre-defined panel rated each item on an ordinal 4-point Likert scale concerning its relevancy, clarity, and simplicity for individual-CVI calculation. The mean individual-CVI was considered as the Scale-CVI for each domain. Twenty lay experts (selected from the target population) were asked to express their opinion on each item's importance by scoring on a 5-point Likert scale; subsequently, face validity was determined by the impact score formula. The questions that had minimum values of CVR, CVI, and impact score were retained in the final version of the questionnaire for reliability evaluation. Construct validity was evaluated via Confirmatory Factor Analysis. Internal consistency and test-retest reliability were checked using Cronbach's α and intraclass correlation coefficients (ICC). Fifty-four patients recruited based on inclusion and exclusion criteria to participate in the reliability analysis.
All the questions received the qualified values of CVR (exceeding 0.49 points) and impact score (more than 1.5 points) and were retained in the questionnaire; however, revisions were made for questions with a CVI 0.7-0.9 for clarity and simplicity. The result demonstrated relative goodness CFA and proper internal consistency, as Cronbach's α coefficient was 0.964 for the test (0.845 and 0.963 for the first and second part of the questionnaire, respectively (and 0.888 for the re-test (0.793 and 0.876 for the first and second section of the questionnaire, respectively). The ICC values between test and re-test for the first and second part and the whole questionnaire were obtained as 0.904, 0.922, and 0.921, respectively.
The Persian version of the IBD-F questionnaire was valid and reliable; thus, an appropriate scale was deemed to measure fatigue (severity, frequency, and impact on daily activities).
Pancreatic cancer (PC) is an aggressive disease with a high mortality and poor prognosis. The human microbiome is a key factor in many malignancies, having the ability to alter host metabolism and ...immune responses and participate in tumorigenesis. Gut microbes have an influence on physiological functions of the healthy pancreas and are themselves controlled by pancreatic secretions. An altered oral microbiota may colonize the pancreas and cause local inflammation by the action of its metabolites, which may lead to carcinogenesis. The mechanisms behind dysbiosis and PC development are not completely clear. Herein, we review the complex interactions between PC tumorigenesis and the microbiota, and especially the question, whether and how an altered microbiota induces oncogenomic changes, or vice versa, whether cancer mutations have an impact on microbiota composition. In addition, the role of the microbiota in drug efficacy in PC chemo- and immunotherapies is discussed. Possible future scenarios are the intentional manipulation of the gut microbiota in combination with therapy or the utilization of microbial profiles for the noninvasive screening and monitoring of PC.
To date, there is no licensed treatment or approved vaccine to combat the coronavirus disease of 2019 (COVID-19), and the number of new cases and mortality multiplies every day. Therefore, it is ...essential to develop an effective treatment strategy to control the virus spread and prevent the disease. Here, we summarized the therapeutic approaches that are used to treat this infection. Although it seems that antiviral drugs are effective in improving clinical manifestation, there is no definite treatment protocol. Lymphocytopenia, excessive inflammation, and cytokine storm followed by acute respiratory distress syndrome are still unsolved issues causing the severity of this disease. Therefore, immune response modulation and inflammation management can be considered as an essential step. There is no doubt that more studies are required to clarify immunopathogenesis and immune response; however, new therapeutic approaches including mesenchymal stromal cell and immune cell therapy showed inspiring results.
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