Investigation of Fibroblast Growth Factor Peptide Antagonist on Mouse Model Breast Tumor through ERK/MAPK and PI3K/AKT Signaling Pathways.

BACKGROUND: In the majority of cancers, metastasis of tumor cells is the main cause of treatment failure. This study intended to investigate the effectiveness of basic fibroblast growth factor (bFGF) peptide designed to inhibit tumor growth in 4T1 metastatic breast cancer through the PI3K/AKT and ERK/MAPK signal transduction pathways. METHODS: The tumor was induced through 4T1 tumor graft in BALB/c mice. The designed peptide was injected intraperitoneal at three selected doses after two weeks for 14 days. The PBS and doxorubicin were used as the negative and positive control groups, respectively. Tumor size was measured and after the treatment period, the mice underwent a surgery and tumors were used for the western blot examinations. RESULTS: the peptide injection was effective in reducing or inhibiting tumor growth in mice model and in vitro. The western blot analysis results showed that the p-AKT and p-ERK levels in peptide treated tumors were reduced (p<0.05). CONCLUSION: The peptide injection was effective in mice model. Findings showed that in the two signal transduction pathways, the p-AKT and p-ERK levels were significantly different from the negative control group.

Time-related meal patterns and breakfast quality in a sample of Iranian adults.

BACKGROUND: Some evidence shows that meal timing is associated with diet quality. We aimed to investigate the relationship between meal timing and breakfast quality in a sample of Iranian adults. METHODS: This cross-sectional study was conducted on 850 men and women living in Tehran, Iran. Dietary data was recorded by three non-consecutive 24-h dietary recalls. The Breakfast Quality Index (BQI) was calculated. Time-related meal patterns included the interval between the first and last meal (eating and fasting window), frequency of meals, length of sleep, and time of first and last eating occasion. The multiple linear regression analysis was used to identify the relationships between time-related meal patterns and BQI. RESULTS: The mean (95% CI) of BQI was 4.52 (4.45-4.65) and the maximum was 8. Bread, cheese, vegetables, fruits, energy, and carbohydrate intake showed positive associations with BQI scores. Longer fasting time showed a positive association with fruits (ß (CI 95%)) (0.11 (0.0003-0.005), and vegetable consumption (0.12 (0.009-0.07)) and BQI score (0.39 (0.001-0.06)). Time of first eating occasions indicated a negative association with protein and fat intake and BQI score. Time of last eating occasions showed a positive association with vegetables consumption and BQI score. The longer length of sleep was associated with a higher BQI score. The frequency of meals was significantly and positively related to energy and macronutrients intake and BQI. CONCLUSION: Earlier first and last meal, longer sleep length, longer fasting window, and a greater meal frequency were associated with a better breakfast quality.

Global prevalence and genotype distribution of norovirus infection in children with gastroenteritis: A meta-analysis on 6 years of research from 2015 to 2020.

In the post rotavirus vaccine era, norovirus (NoV) plays an increasingly important role in epidemic and sporadic gastroenteritis among children. This study was designed to provide an updated meta-analytic review of the prevalence of NoV among paediatric patients with gastroenteritis and to clarify the relationship between NoV infection and gastroenteritis. Systematic searches of the literature for potentially relevant studies were carried out from 1 January 2015 to 29 May 2020. The inverse variance method was chosen for weighting of the studies, and the random-effects model was used to analyse data. To determine the association between NoV infection and gastroenteritis in children, pooled odds ratio (OR) and its 95% confidence interval (CI) were computed for case-control studies. The pooled prevalence of NoV infection among 12,0531 children with gastroenteritis from 45 countries across the world was 17.7% (95% CI: 16.3%-19.2%). There were 28 studies with a case-control design, and the pooled prevalence of NoV infection among 11,954 control subjects was 6.7% (95% CI: 5.1%-8.8%). The pooled OR of the association of NoV infection and gastroenteritis was 2.7 (95% CI: 2.2-3.4). The most common NoV genotypes were GII.4 (59.3%) and GII.3 (14.9%). The highest frequency of NoV was found in the age group below 1 year. Our findings indicated a substantial burden of gastroenteritis caused by NoV globally, with GII.4 and GII.3 the major genotypes responsible for the majority of NoV-associated gastroenteritis cases among children. Younger age and male sex can be considered risk factors for NoV-associated gastroenteritis among children.

Designing a Logistic Regression Model for a Dataset to Predict Diabetic Foot Ulcer in Diabetic Patients: High-Density Lipoprotein (HDL) Cholesterol Was the Negative Predictor.

OBJECTIVES: Although the risk factors for diabetic neuropathy and diabetic foot ulcer have been detected, there was no practical modeling for their prediction. We aimed to design a logistic regression model on an Iranian dataset to predict the probability of experiencing diabetic foot ulcers up to a considered age in diabetic patients. METHODS: The present study was a statistical modeling on a previously published dataset. The covariates were sex, age, body mass index (BMI), fasting blood sugar (FBS), hemoglobin A1C (HbA1C), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride (TG), insulin dependency, and statin use. The final model of logistic regression was designed through a manual stepwise method. To study the performance of the model, an area under receiver operating characteristic (AUC) curve was reported. A scoring system was defined according to the beta coefficients to be used in logistic function for calculation of the probability. RESULTS: The pretest probability for the outcome was 30.83%. The final model consisted of age (ß1 = 0.133), BMI (ß2 = 0.194), FBS (ß3 = 0.011), HDL (ß4 = -0.118), and insulin dependency (ß5 = 0.986) (P < 0.1). The performance of the model was definitely acceptable (AUC = 0.914). CONCLUSION: This model can be used clinically for consulting the patients. The only negative predictor of the risk is HDL cholesterol. Keeping the HDL level more than 50 (mg/dl) is strongly suggested. Logistic regression modeling is a simple and practical method to be used in the clinic.

An ecological modeling on the adjusted effects of socioeconomic determinants and HLA-DRB1 alleles in fatality of COVID-19 during the early phase of epidemics in a group of countries.

INTRODUCTION: Socioeconomic determinants along with genetic status may affect fatality rate of COVID-19. We intend to investigate the adjusted effects of the HLA-DRB1 alleles and socioeconomic determinants including gross domestic product per capita (GDP cap) and health expenditure per capita (HE cap) in fatality of COVID-19 during the early phase of epidemic in a group of countries. METHODS: As an ecological study, early exposure to epidemics was defined as having more than 5000 confirmed cases of COVID-19 from 1 March 2020 to 1 April 2020. Poisson regression was used to report adjusted incidence rate ratio (IRR) for case fatality rate in this constant time period. RESULTS: Fourteen countries were eligible. Among the alleles, DR7 showed the strongest risk factor (IRR=112.535, P<0.001). Having GDP cap more than 40000$ or having HE cap more than 3000$ was a protecting factor (IRR=0.899, P<0.001, adjusted with allele DR7). Having GDP cap more than 40000$ along with having HE cap more than 3000$ was a protecting factor (IRR=0.471, P<0.001, adjusted with allele DR7). CONCLUSION: Socioeconomic status of the countries may compensate the probable harmful effect of some HLA-DRB1 alleles. This conclusion was limited to a period that all the selected countries had almost similar governmental intervention.

Determination of Serum Levels of Interleukin-6, Interleukin-8, Interleukin-10, and Tumor Necrosis-Alpha and their Relationship With The Total Body Surface Area in Children.

There are few studies on the inflammatory processes and the role of cytokines involved in pediatric burn injuries. The present study aims to measure the serum levels of cytokines and their relationship with the degree of burn injury in children. Within the 48 hours of hospitalization, the serum samples were obtained to measure inflammatory cytokines (interleukin-6, interleukin-8, interleukin-10 [IL-6, IL-8, and IL-10] and tumor necrosis factor-alpha [TNF-α]). The level of all of these cytokine factors was assessed by enzyme-linked immunosorbent assay technique. The mean levels of IL-6, IL-8, IL-10, and TNF-α was 18.15 ± 4.77 pg/ml, 59.54 ± 4.59 pg/ml, 8.41 ± 2.09 pg/ml, and 1.48 ± 0.15 pg/ml, respectively, which were higher than the normal range designated for the healthy pediatrics age group. The levels of TNF-α were higher in patients with sepsis (P = .03) and deceased patients (P = .001). There was a statistically significant difference in the levels of IL-8 in patients with second- (.001) and third-degree (.001) burn injuries in comparison to the first-degree burn injuries, and the level of IL-8 was statistically significantly higher in patients with electrical burn injuries in comparison to scald burn injuries (.01). IL-10 was statistically significantly higher in patients with contact burn injuries in comparison to scald (.001) and flame (.03) burn injuries. Cytokine levels in pediatric burn patients increased after severe burn injuries. There was a significant correlation between the levels of IL-8 and the degree of burn injuries.

A Fibroblast Growth Factor Antagonist Peptide Inhibits Breast Cancer in BALB/c Mice.

OBJECTIVE: Given the role of basic fibroblastic growth factor (bFGF) in tumor growth, it has been considered as a potential target for tumor therapy. In this study, we investigate the effect of bFGF antagonistic peptide on the growth and angiogenesis of 4T1 mammary carcinoma tumor (MCT) in BALB/c mice. METHODS: An engineered peptide was injected into BALB/c mice in doses of 1, 2.5, 5 and 10 mg/kg daily for 14 days. Immunohistochemical analysis using anti-CD31 and anti-CD34 were conducted as indices of angiogenesis. In addition, blood samples were taken from the eyes of treated and control mice and the levels of Interleukin-8 (IL-8) and Tumor Necrosis Factor-α (TNF-α) were measured by ELISA. Data was analyzed by ANOVA using SPSS. RESULTS: The antagonistic peptide inhibited growth and angiogenesis of MCT (P ≤0.05), and decreased the serum level of IL-8 and TNF-α in treated groups compared to the control groups. CONCLUSION: The inhibition of tumor angiogenesis has been considered as an important strategy to halt tumor growth. The results of current study confirm that the antiangiogenic peptide effectively inhibited the growth of MCT, and shows potential for clinical trials for the treatment of cancer in humans.

Small ubiquitin-like modifier 4 M55V polymorphism is not associated with diabetic nephropathy in Iranian type 2 diabetes patients.

INTRODUCTION: We studied the impact of small ubiquitin-like modifier 4 (SUMO4) M55V polymorphism on susceptibility to diabetic nephropathy in Iranian type 2 diabetes patients. MATERIALS AND METHODS: The patient group consisted of 50 Iranian type 2 diabetes patients with nephropathy, and the control group consisted of 50 Iranian type 2 diabetes patients without nephropathy. Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism method for the M55V. RESULTS: The frequency of SUMO4 AA, AG, and GG genotypes were 23%, 18%, and 9% in the patient group and 10%, 22%, and 18% in the control group. There was no significant difference in frequency of SUMO4 genotypes in patients compared to controls. CONCLUSION: These findings indicate that SUMO4 M55V polymorphism is not associated with diabetic nephropathy in Iranian type 2 diabetes patients.

Systemic sclerosis: demographic, clinical and serological features in 100 Iranian patients.

To evaluate demographic, clinical and laboratory features associated with scleroderma-specific auto-antibodies. Sera of 100 patients with systemic sclerosis (SSc) were analyzed by an indirect immunofluorescence technique with HEp-2 cells as a substrate. Specific ANA such as anti-centromere antibodies (ACA), anti-topoisomerase (TOPO), anti-RNA polymerase III (Pol 3), anti-U3-RNP (U3-RNP), anti-Th/To (Th/To) and anti-PM/Scl (PM/Scl) were detected by line immunoassay and anti-U1-RNP (U1-RNP) by ELISA. Frequency of clinical features associated with a specific antibody group was reported cumulatively over the follow-up period. Frequency of specific clinical features was compared across the two disease subtype including limited cutaneous (lcSSc) or diffuse cutaneous (dcSSc) as well as the auto-antibody groups. Ninety-four percent of patients were ANA positive with significant higher skin score, Raynauds and digital ulcer/gangrene. Anti-TOPO was detected in 71% of all patients, in 90.5% of dcSSC and in 65.8% of lcSSc. Anti-TOPO was significantly associated with dcSSc, higher skin score, digital ulcer/gangrene, pulmonary fibrosis, DLCO <70%. U1-RNP antibody was associated with lower fibrosis in lung. ACA was positive in 7% of patients and exclusively in those with lcSSc. We did not find association between gender and presence of auto-antibodies. Anti-TOPO antibody had a high prevalence in contrast to low prevalence of ACA antibody. There were no differences in clinical subtypes of the disease in patients with positive anti-TOPO and positive ACA. Differences in prevalence of auto-antibodies are suggestive of further genetic study.

No association of the SUMO4 polymorphism M55V variant in type 2 diabetes in Iranian subjects.

INTRODUCTION: Diabetes mellitus incidence has an increasing rate and it's genetic aspect is an important approach as a risk factor and predictive value in this disorder. In some population, SUMO4, a regulator of NF-κB, gene polymorphism is associated with diabetes. A single-nucleotide polymorphism was detected in SUMO4; substituting a highly conserved methionine with a valine residue (M55V). We studied the association between M55V polymorphism in the SUMO4 gene insusceptibility of type 2 diabetes in patients with type 2 diabetes. MATERIALS AND METHODS: Participants were 50 patients with type 2 diabetes and 50 control Iranian subjects. Genotyping was done using polymorphism chain reaction (PCR) technique and subsequent cleavage by restriction endonuclease (RFLP) for the M55V SUMO4 gene variant. RESULTS: The frequency of SUMO4 AA, AG and GG were 13%, 25% and 12% in control group and 20%, 22%, 18% in the type 2 diabetes patients respectively. The SUMO4 M55V variant was not associated with the susceptibility of type 2 diabetes. CONCLUSION: The study indicates that the SUMO4 gene M55V variant was not associated with the susceptibility of the type 2 diabetes polymorphism.