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"Ferns, Gordon"
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Machine learning algorithms reveal potential miRNAs biomarkers in gastric cancer
2023
Gastric cancer is the high mortality rate cancers globally, and the current survival rate is 30% even with the use of combination therapies. Recently, mounting evidence indicates the potential role of miRNAs in the diagnosis and assessing the prognosis of cancers. In the state-of-art research in cancer, machine-learning (ML) has gained increasing attention to find clinically useful biomarkers. The present study aimed to identify potential diagnostic and prognostic miRNAs in GC with the application of ML. Using the TCGA database and ML algorithms such as Support Vector Machine (SVM), Random Forest, k-NN, etc., a panel of 29 was obtained. Among the ML algorithms, SVM was chosen (AUC:88.5%, Accuracy:93% in GC). To find common molecular mechanisms of the miRNAs, their common gene targets were predicted using online databases such as miRWalk, miRDB, and Targetscan. Functional and enrichment analyzes were performed using Gene Ontology (GO) and Kyoto Database of Genes and Genomes (KEGG), as well as identification of protein–protein interactions (PPI) using the STRING database. Pathway analysis of the target genes revealed the involvement of several cancer-related pathways including miRNA mediated inhibition of translation, regulation of gene expression by genetic imprinting, and the Wnt signaling pathway. Survival and ROC curve analysis showed that the expression levels of hsa-miR-21, hsa-miR-133a, hsa-miR-146b, and hsa-miR-29c were associated with higher mortality and potentially earlier detection of GC patients. A panel of dysregulated miRNAs that may serve as reliable biomarkers for gastric cancer were identified using machine learning, which represents a powerful tool in biomarker identification.
Journal Article
A high consumption of tomato and lycopene is associated with a lower risk of cancer mortality: results from a multi-ethnic cohort
2020
We investigated the association between the consumption of tomato and lycopene and cancer mortality among US adults.
Prospective.
The National Health and Nutrition Examination Survey (1999-2010).
Participants with estimated dietary data on tomato and lycopene consumption were included. Outcome data up until 31 December 2011 were also ascertained. Cox proportional hazard regression models were used to relate baseline tomato and lycopene consumption with cancer mortality. We conducted a competing-risk survival analysis to account for deaths from other causes.
Adjusted Cox models showed that tomato and lycopene intake were inversely related (hazard ratio (95 % CI)) to cancer mortality: 0·86 (0·81, 0·92) and 0·79 (0·74, 0·82), respectively. In the adjusted competing-risk models, the sub-hazard ratios (95 % CI) were 0·89 (0·83, 0·94) and 0·82 (0·78, 0·86) for cancer mortality for tomato and lycopene intake, respectively. No significant interaction was found for the association between tomato and lycopene consumption and cancer mortality while comparing older (aged >50 years) v. younger adults (Pinteraction > 0·173 for all) and obese v. non-obese (Pinteraction > 0·352 for all).
Our results demonstrate the potential beneficial effects of a high dietary intake of tomato and lycopene on cancer death. Further prospective studies are needed to explore the association.
Journal Article
Prediction of serum anti-HSP27 antibody titers changes using a light gradient boosting machine (LightGBM) technique
2023
Previous studies have proposed that heat shock proteins 27 (HSP27) and its anti-HSP27 antibody titers may play a crucial role in several diseases including cardiovascular disease. However, available studies has been used simple analytical methods. This study aimed to determine the factors that associate serum anti-HSP27 antibody titers using ensemble machine learning methods and to demonstrate the magnitude and direction of the predictors using PFI and SHAP methods. The study employed Python 3 to apply various machine learning models, including LightGBM, CatBoost, XGBoost, AdaBoost, SVR, MLP, and MLR. The best models were selected using model evaluation metrics during the K-Fold cross-validation strategy. The LightGBM model (with RMSE: 0.1900 ± 0.0124; MAE: 0.1471 ± 0.0044; MAPE: 0.8027 ± 0.064 as the mean ± sd) and the SHAP method revealed that several factors, including pro-oxidant-antioxidant balance (PAB), physical activity level (PAL), platelet distribution width, mid-upper arm circumference, systolic blood pressure, age, red cell distribution width, waist-to-hip ratio, neutrophils to lymphocytes ratio, platelet count, serum glucose, serum cholesterol, red blood cells were associated with anti-HSP27, respectively. The study found that PAB and PAL were strongly associated with serum anti-HSP27 antibody titers, indicating a direct and indirect relationship, respectively. These findings can help improve our understanding of the factors that determine anti-HSP27 antibody titers and their potential role in disease development.
Journal Article
Impact of Probiotic Administration on Serum C-Reactive Protein Concentrations: Systematic Review and Meta-Analysis of Randomized Control Trials
by
Mazidi, Mohsen
,
Rezaie, Peyman
,
Ferns, Gordon
in
C-Reactive Protein - metabolism
,
Databases, Factual
,
Humans
2017
We conducted this systematic review and meta-analysis of prospective studies to determine the effect of probiotic administration on serum C-reactive protein (CRP) concentrations. We searched PubMed-Medline, Web of Science, the Cochrane, and Google Scholar databases (until May 2016) to identify prospective studies evaluating the impact of probiotic administration on CRP. We used a random effects models and generic inverse variance methods to synthesize quantitative data, followed by a leave-one-out method for sensitivity analysis. The systematic review registration number was: CRD42016039457. From a total of 425 entries identified via searches, 20 studies were included in the final analysis. The meta-analysis indicated a significant reduction in serum CRP following probiotic administration with a weighted mean difference (WMD) of −1.35 mg/L, (95% confidence interval (CI) −2.15 to −0.55, I2 65.1%). The WMDs for interleukin 10 (IL10) was −1.65 pg/dL, (95% CI −3.45 to 0.14, I2 3.1%), and −0.45 pg/mL, (95% CI −1.38 to 0.48, I2 10.2%) for tumor necrosis factor alpha (TNF-α). These findings were robust in sensitivity analyses. This meta-analysis suggests that probiotic administration may significantly reduce serum CRP while having no significant effect on serum IL10 and TNF-α.
Journal Article
Heavy Metal Poisoning and Cardiovascular Disease
2011
Cardiovascular disease (CVD) is an increasing world health problem. Traditional risk factors fail to account for all deaths from CVD. It is mainly the environmental, dietary and lifestyle behavioral factors that are the control keys in the progress of this disease. The potential association between chronic heavy metal exposure, like arsenic, lead, cadmium, mercury, and CVD has been less well defined. The mechanism through which heavy metals act to increase cardiovascular risk factors may act still remains unknown, although impaired antioxidants metabolism and oxidative stress may play a role. However, the exact mechanism of CVD induced by heavy metals deserves further investigation either through animal experiments or through molecular and cellular studies. Furthermore, large-scale prospective studies with follow up on general populations using appropriate biomarkers and cardiovascular endpoints might be recommended to identify the factors that predispose to heavy metals toxicity in CVD. In this review, we will give a brief summary of heavy metals homeostasis, followed by a description of the available evidence for their link with CVD and the proposed mechanisms of action by which their toxic effects might be explained. Finally, suspected interactions between genetic, nutritional and environmental factors are discussed.
Journal Article
Communication skills training for physicians improves health literacy and medical outcomes among patients with hypertension: a randomized controlled trial
by
Peyman, Nooshin
,
Behzhad, Fatemeh
,
Tavakoly Sany, Seyedeh Belin
in
Adult
,
Aged
,
Aged, 80 and over
2020
Background
Improving the training of physicians about communication skills and patient health literacy (HL) is a major priority that remains an open question. We aimed to examine the effectiveness of communication skills training for physicians on the hypertension outcomes and the health literacy skills, self-efficacy and medication adherence in patients with uncontrolled blood pressure (BP).
Methods
A randomized, controlled trial method was conducted on 240 hypertensive patients and 35 physicians presenting to healthcare clinics in the Mashhad, Iran, from 2013 to 2014. Using stratified blocking with block sizes of 4 and 6, eligible patients with uncontrolled blood pressure were randomly allocated to the intervention and control groups. Physicians in the intervention group received educational training over 3 sessions of Focus –Group Discussion and 2 workshops. The control group received the routine care. The primary outcome was a reduction in systolic and diastolic BP from baseline to 6 months. The secondary outcome was promoting HL skills in hypertensive patients. Data were analyzed using the regression model and bivariate tests.
Results
After the physician communication training, there was a significant improvement in physicians-patient communication skills, hypertension outcomes, medication adherence, and self-efficacy among the patients being managed by the physicians receiving training, compared to the control group.
Conclusion
The educational intervention leads to better BP control; it may have been sufficient training of physicians change to impact counseling, HL and self-efficacy and adherence. The quality of physician-patient communication is an important modifiable element of medical communication that may influences health outcomes in hypertensive Iranian patients.
Trial registration
Iranian Registry of Clinical Trials (IRCT),
IRCT20160710028863N24
. Registered April 4, 2018 [retrospectively registered].
Journal Article
Dyslipidemia and cardiovascular disease risk among the MASHAD study population
by
Zare-Feyzabadi, Reza
,
Ghaffari, Mohammad-Seddigh
,
Besharatlou, Mohammad-Reza
in
Angina pectoris
,
Anticholesteremic agents
,
Antihypertensives
2020
Introduction
Dyslipidemia may be defined as increased levels of serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), or a decreased serum high-density lipoprotein cholesterol (HDL-C) concentration. Dyslipidemia is an established risk factor for cardiovascular disease (CVD). We aimed to investigate the association of dyslipidemia and CVD events among a population sample from Mashhad, in northeastern Iran.
Material and methods
This prospective cohort study comprised a population of 8698 men and women aged 35–65 years who were recruited from the Mashhad Stroke and Heart Atherosclerotic Disorder (MASHAD) study. Socioeconomic and demographic status, anthropometric parameters, laboratory evaluations, lifestyle factors, and medical history were gathered through a comprehensive questionnaire and laboratory and clinical assessment for all participants. Cox regression model and 95% confidence interval (CI) were used to evaluate the association of dyslipidemia and its components with CVD incidence.
Results
After 6 years of follow-up, 233 cases of CVD (including 119 cases of unstable angina [US], 74 cases of stable angina [SA], and 40 cases of myocardial infarction [MI]) were identified in the study population. Unadjusted baseline serum LDL-C, TC, and TG levels were positively associated with the risk of total CVD events among the entire population (HR: 1.54, 95% CI: 1.19–2;
P
-value< 0.01; HR: 1.53; 95% CI: 1.18–1.98;
P
< 0.01; HR: 1.57; 95% CI: 1.27–2.03; P < 0.01, respectively). However, after adjusting for confounding factors (age, body mass index [BMI], family history of CVD, smoking status [non-smoker, ex-smoker and current smoker], lipid lowering drug treatment, anti-hypertensive drug treatment, hypertension, healthy eating index [HEI], total energy intake, and presence of diabetes mellitus), a significant direct association only remained between TC and MI risk in men (HR: 2.71; 95%CI: 1.12–6.57;
P
-value< 0.05).
Conclusion
In the present study, TC baseline level was significantly associated with the risk of MI among men.
Journal Article
The role of cancer-associated fibroblasts and exosomal miRNAs-mediated intercellular communication in the tumor microenvironment and the biology of carcinogenesis: a systematic review
by
Ranjbar, Maryam
,
Haghjooy Javanmard, Shaghayegh
,
A. Ferns, Gordon
in
631/67/327
,
692/699/67/327
,
Apoptosis
2024
CAFs (cancer-associated fibroblasts) are highly flexible cells of the cancer microenvironment. They produce the extracellular matrix (ECM) constituents that form the structure of the tumor stroma but are also a source of metabolites, growth factors, chemokines, and exosomes that impact every aspect of the tumor, including its response to treatment. It is believed that exosomal miRNAs facilitate intercellular signaling, which is essential for the development of cancer. The role of miRNAs and CAFs in the tumor microenvironment (TME) and carcinogenesis is reviewed in this paper. The preferred reporting items for systematic reviews and meta-analyses (PRISMA) 2020 guidelines were used to perform a systematic review. Several databases, including Web of Science, Medline, Embase, Cochrane Library, and Scopus, were searched using the following keywords: CAFs, CAF, cancer-associated fibroblasts, stromal fibroblasts, miRNA, exosomal miRNAs, exosome and similar terms. We identified studies investigating exosomal miRNAs and CAFs in the TME and their role in carcinogenesis. A total of 12,572 papers were identified. After removing duplicates (
n
= 3803), 8774 articles were screened by title and abstract. Of these, 421 were excluded from further analysis. It has been reported that if exosomal miRNAs in CAFs are not functioning correctly, this may influence the secretory phenotype of tip cells and contribute to increased tumor invasiveness, tumor spread, decreased treatment efficacy, and a poorer prognosis. Under their influence, normal fibroblasts (NFs) are transformed into CAFs. Furthermore, they participate in metabolic reprogramming, which allows for fast proliferation of the cancer cell population, adaptation to growing energy demands, and the capacity to avoid immune system identification.
Journal Article
A Mediterranean diet is associated with improved total antioxidant content of human breast milk and infant urine
by
Zarban, Asghar
,
Naseri, Mohsen
,
Karbasi, Samira
in
antioxidant activity
,
Antioxidant content
,
Antioxidants
2023
Background
The composition of breast milk (BM) is dynamic and can be influenced by maternal variables that include the diet and nutritional status. This study examined the association between maternal adherence to a Mediterranean diet (MedDiet) and total antioxidant content of BM and infant urine.
Methods
We collected 350 BM samples from mothers and urine samples from their infants. The dietary intakes of the mothers were recorded using a validated 65 items-food frequency questionnaire (FFQ). The total antioxidant status of the samples was assessed using the ferric reducing/antioxidant power (FRAP), the 1, 1-diphenyl-2-picrylhydrazyl (DPPH), thiobarbituric acid reactive substances (TBARS), and thiol quantification assays. Milk protein, calcium, and triglyceride (TG) were also determined using standard biochemical kits.
Results
Subjects with the highest MedDiet scores were among the women in the highest tertile (T3) for consumption of dietary fiber, fruits, vegetables, nuts, legumes, and seeds, low-fat dairy, whole grains, and the lowest consumption of red meat, sweetened beverages, and sodium, compared to women in the first tertile (T1) with the lowest MedDiet scores. After adjustment for potential confounders, the individuals in the highest tertile for MedDiet score had a significantly higher level of milk DPPH, and infant urinary DPPH than the lowest tertile and had a significantly higher level of milk protein, FRAP and infant urinary FRAP compared to the T2 (
P
< 0.05). In addition, the mothers in the T3 for the MedDiet pattern had a significantly lower level of milk TG compared to those within the T1 (
P
< 0.05).
Conclusion
Our findings show that a high maternal adherence to a MedDiet can affect BM composition and their infants' urine.
Journal Article
The lower expression of circulating miR‐210 and elevated serum levels of HIF‐1α in ischemic stroke; Possible markers for diagnosis and disease prediction
2021
Background Stroke, either due to ischemia or hemorrhage, causes acute neurological damages to the brain. There is shortage of reliable biomarkers for ischemic stroke (IS), and we therefore investigated the serum concentrations of microRNA‐210 (miR‐210) and hypoxia inducible factor‐1α (HIF‐1α), as possible diagnostic and/or prognostic markers for IS. Methods Serum samples were acquired from 52 IS patients and their healthy counterparts at five time points: upon admission, 24 and 48 h after admission, upon discharge and 3 months later. Serum levels of miR‐210 and HIF‐1α were respectively analyzed using real time RT‐PCR and ELISA. Diagnostic and prognostic accuracy tests were performed to assess the value of suggested biomarkers. Results IS patients demonstrated higher levels of serum HIF‐1α and lower miR‐210 in comparison to the healthy subjects. MiR‐210 was suggested to be a weak diagnostic biomarker at the time of admission (AUC = 0.61; p = 0.05), while HIF‐1α was an acceptable diagnostic marker for IS (AUC = 0.73; p < 0.0001). The higher expression of miR‐210 and lower levels of HIF‐1α were associated with better survivals in IS patients. Conclusions Serum miR‐210 is a weak diagnostic marker of IS. Serum HIF‐1α is a better biomarker in diagnosing IS patients but further work in larger groups, including those with hemorrhagic stroke is necessary to confirm its diagnostic utility. Similarly, the prognostic potentiality of miR‐210 and HIF‐1α was acceptable but needs bigger sample size and longer follow‐up to be statistically confirmed. Here, we investigated the serum concentrations of miR‐210 and HIF‐1α, as possible diagnostic and/or prognostic markers for ischemic stroke (IS). IS patients demonstrated higher levels of serum HIF‐1α and lower miR‐210 in comparison to the healthy subjects. MiR‐210 was suggested to be a weak diagnostic biomarker at the time of admission (AUC = 0.61; p = 0.05), while HIF‐1α was an acceptable diagnostic marker for IS (AUC = 0.73; p < 0.0001). The higher expression of miR‐210 and lower levels of HIF‐1α were associated with better survivals in IS patients.
Journal Article