Time to take HPV infection in colorectal cancer patients more seriously.

Background: The association between viral infections and colorectal cancer (CRC) remains an enigma in cancer research. Certain types of Human Papillomaviruses (hr-HPVs), known for their oncogenic properties, have been observed in particular CRC biopsies, further adding to the enigma surrounding this association. Materials and methods: This cross-sectional study was conducted on 40 confirmed cases of CRC adenocarcinoma. The presence and genotyping of HPV DNA in colorectal fresh tissue and urine samples was assessed using an HPV DNA hybridization kit. A subset of serum samples from both CRC cases and healthy volunteers was randomly chosen and subjected to western blot to investigate the presence of HPV16 E6/E7 oncoproteins carried by exosomes. Results: It was observed that 26/40 HPV-positive CRC patients demonstrated 7 times more chance to develop colorectal cancer when compared to those 8/40 normal tissue (odds ratio [OR] = 7.4; confidence interval [CI] 95% = 0.483156-0.793718; p < 0.001). Of 26 HPV-positive CRC patients, 14 urine samples were also showed HPV DNA positivity (p = 0.013). High-risk HPV16 was the most prevalent genotype detected in both 24/40 tumor and 12/40 urine samples (p < 0.001). The tumor sample of a male was HPV45, while another male's urine sample was HPV31. A female CRC patient had HPV83 in tumor and HPV56 in urine. Here, was the first detection of HPV83 in a CRC patient. Notably among 20 randomly selected serum exosome samples, one serum sample concurrently tested positive for both HPV16 E6 and E7 oncoproteins, and one sample tested positive for HPV16 E7 oncoprotein. Conclusion: High risk HPV DNA detection in CRC urine samples supports non-invasive screening tools. Detection of HPV16 E6 and E7 oncoproteins in exosomes from serum samples shows potential for non-invasive diagnostics. HPV's potential role in CRC development is also underscored. HPV vaccination should be implemented in low- and middle-income countries to prevent cancer.

Health risk assessment for consuming rice, bread, and vegetables in Hoveyzeh city.

Introduction: People are continuously exposed to contamination, which mainly consists of heavy metals (HMs) and organic compounds. Several metals can get into grains, veggies, and bread through various methods. We estimated the health risk of HM exposure from the consumption of bread, veggies, and rice, considering the per capita amounts of these foods in the Iranian food basket, especially in Hoveyzeh and Azadegan Plain. Material and method: The food products analyzed for the assessment of HMs include different veggies, rice, and bread. The health risk assessment was done with the Hazard Quotient and cancer risk formulae. The buying of vegetables, rice, and bread was done in random order during the fall and wintertime seasons. Result: Tarom rice has the maximum reported levels of Cd (0.55 mg/kg), but Pakistani rice has the lowest level (0.18 mg/kg). Radish shows the highest concentrations of As, Pb, Cr, and Ni among vegetation, while Cress shows the lowest level. The study findings showed that Lavash bread had the highest levels of As (1.31 mg/kg), Cd (0.2 mg/kg), and Ni (1.2 mg/kg), whereas it indicated the lowest level of Cr (0.056 mg/kg). While the non-carcinogenic risk of HMs was evaluated between two groups of adults and children, both groups' HI and HQ levels were less than 1. The maximum HQ and HI scores for children were associated with Arsenic (As), specifically 0.0127 and 0.0137 for Tarom rice, respectively. Nevertheless, the highest HQ and HI scores for adults were associated with As, namely 0.0059 and 0.0064 for Tarom rice, respectively. Conclusion: The evaluation of the carcinogenic risk caused by HM exposure in kids and adults showed that both groups' accumulated lifetime CRs and ILCRs were lower than 1*10-6. Hence, the consumption of veggies, rice, and bread within the study's area does not show an association with the occurrence of chronic diseases resulting from hazardous HMs.

The effect of breastfeeding on children's growth indices up to 6 months: An application of multivariate t linear mixed model.

Background: This study aimed to determine the effect of breastfeeding on children's growth indices. Materials and Methods: Longitudinal data of children's growth (height, weight, and head circumference) were as a dependent variable and type of nutrition as an independent variable with using multivariate t linear mixed model. Results: The indicated that the height, weight, and head circumference of infants who were fed with breast milk showed a statistically significant difference (P < 0.05) with those of infants receiving formula. Conclusion: Exclusive feeding with breast milk, especially in the first 6 months of life, has a significant impact on the child's growth indicators compared to formula or, or a combination of both.

Association of the corona virus (Covid-19) epidemic with environmental risk factors.

The current outbreak of the novel coronavirus SARS-CoV-2 (coronavirus disease 2019; previously 2019-nCoV), epicenter in Hubei Province (Wuhan), People's Republic of China, has spread too many other countries. The transmission of the corona virus occurs when people are in the incubation stage and do not have any symptoms. Therefore, the role of environmental factors such as temperature and wind speed becomes very important. The study of Acute Respiratory Syndrome (SARS) indicates that there is a significant relationship between temperature and virus transmission and three important factors, namely temperature, humidity and wind speed, cause SARS transmission. Daily data on the incidence and mortality of Covid-19 disease were collected from World Health Organization (WHO) website and World Meter website (WMW) for several major cities in Iran and the world. Data were collected from February 2020 to September 2021. Meteorological data including temperature, air pressure, wind speed, dew point and air quality index (AQI) index are extracted from the website of the World Meteorological Organization (WMO), The National Aeronautics and Space Administration (NASA) and the Moderate Resolution Imaging Spectroradiometer (MODIS) sensor. Statistical analysis carried out for significance relationships. The correlation coefficient between the number of infected people in one day and the environmental variables in the countries was different from each other. The relationship between AQI and number of infected was significant in all cities. In Canberra, Madrid and Paris, a significant inverse relationship was observed between the number of infected people in one day and wind speed. There is a significant positive relationship between the number of infected people in a day and the dew point in the cities of Canberra, Wellington and Washington. The relationship between the number of infected people in one day and Pressure was significantly reversed in Madrid and Washington, but positive in Canberra, Brasilia, Paris and Wuhan. There was significant relationship between Dew point and prevalence. Wind speed showed a significant relationship in USA, Madrid and Paris. AQI was strongly associated with the prevalence of covid19. The purpose of this study is to investigate some environmental factors in the transmission of the corona virus.

Prediction of maximal oxygen uptake based on anthropometric indices in Iranian male adults.

BACKGROUND: Assessment of maximal oxygen consumption is important in both general community and occupational settings. Validity and reliability tests are needed to indicate the functionality of the cardiopulmonary system. OBJECTIVE: This study aimed to establish a maximal oxygen consumption (VO2max) prediction model using anthropometric and demographic variables for young adults in Iran. METHODS: This cross-sectional study was conducted on 64 healthy young men aged 19-29 years. Oxygen consumption was measured directly and the prediction models to estimate VO2max were determined by multiple linear regression. The accuracy of the prediction models was considered using regression coefficient (R), coefficient of determination (R2), and standard error of estimate (SEE). RESULTS: The average VO2max was 44.02±4.31 ml/kg/min. Significant correlations were found between the measured VO2max and the anthropometric and demographic variables (r = 0.16-0.86, P < 0.05). Three significant regression models with acceptable accuracy were developed (R2 = 0.67-0.71, SEE = 3.19-3.21). CONCLUSION: The predictive models consisted of 3-5 variables as significant predictors of VO2max and had acceptable accuracy for Iranian young adults. The proposed models are a simple and valid tool that can be used to estimate the VO2max in the field and in laboratory settings.

Estimation of the effects PM2.5, NO2, O3 pollutants on the health of Shahrekord residents based on AirQ+ software during (2012-2018).

Research objectives: Intertwined with modern life, air pollution is not a new phenomenon. Air pollution imposes a significant number of deaths and disease complications on society, and therefore it is very important to determine the extent of its effects on health in any society. This study sought to evaluate the concentration and short-term and long-term excess mortality attributed to PM2.5, NO2 and O3 observed in Shahrekord. Procedure: Hourly concentrations of PM2.5, O3, and NO2 measured at different stations of the Shahrekord Monitoring Network were obtained from the Shahrekord Department of Environment (DOE). Then, for different air quality monitoring stations, the average 24-hour PM2.5 concentration, the one-hour average NO2 concentration and the maximum 8-hour daily O3 concentration were calculated using Excel 2010. When the maximum 8-hour daily ozone level exceeds 35, it drops below 35 to calculate the SOMO35 index for modeling. Results: The death rates of IHD, COPD, lung cancer and ALRI and stroke related to PM2.5 were 176, 7, 0, 10, 105, respectively. The effect of ozone on respiratory mortality was zero. During the study period in Shahrekord, no respiratory mortality was determined due to ozone and acute lower respiratory tract infection (ALRI). this study is first ever study on health effects of air pollution in shahrekord city. Conclusion: A significant number of deaths due to air pollutants in Shahrekord have been reported. It can be concluded that by designing and implementing strategies and measures to control air pollution, both health effects and economic losses are prevented.

Detection of High-Risk Human Papillomavirus DNA in Invasive Ductal Carcinoma Specimens.

BACKGROUND: According to several studies, there is an association between human papillomavirus (HPV) and breast cancer. Therefore, detection and genotyping of HPV seem important. The present study aimed to investigate the presence of HPV DNA in breast tissues  by analyzing the L1 gene. MATERIALS AND METHODS: This case-control study was conducted on 63 formalin-fixed paraffin-embedded (FFPE) tissues of invasive ductal carcinoma (IDC) as the case group and 32 FFPE tissues of fibroadenoma as the control group. HPV DNA was detected using the polymerase chain reaction assay. Positive samples were then subjected to genotyping. All statistical analyses were performed in SPSS version 22.0. RESULTS: The patients' age ranged from 15 to 92 years, with a mean age of 43.54±16.36 years. HPV DNA was detected in 17/95 (17.89%) samples, including 9/32 (28.12%) fibroadenoma samples and 8/63 (12.69%) IDC samples. No significant difference was observed regarding the presence of HPV DNA between the IDC and fibroadenoma tissues (P=0.08). However, a significant difference was found in the detection of high-risk HPV (HR-HPV) between the case and control groups (P=0.03). In the case group, 87.5% of the detected viruses (7/8 samples) were HR-HPV, while in the control group, 22.22% of positive samples (2/9 samples) were HR-HPV (P=0.03). Based on the results, HR-HPV and low-risk HPV genotypes were detected in 53% (9/17) and 47% (8/17) of positive samples, respectively. CONCLUSION: In this study, 12.69% of IDC samples were positive for HPV genomes, and HR-HPV was detected in 87.5% of these samples. The present results suggest the important role of HR-HPV in the development of breast cancer.

The Association between Diet Quality Scores with Sleep Quality among Employees: A Cross-Sectional Study.

BACKGROUND: Numerous factors such as nutrition and diet can affect the quality of sleep of people, especially employees. The aim of this study was to investigate the relationship between university employees' sleep quality and their dietary quality scores (HEI, DII and DASH score). MATERIALS AND METHODS: This cross-sectional study was performed on 211 employees with a mean age of 38.75±11.31. Nutritional status of individuals was determined through the Food Frequency Questionnaire (FFQ) and to assess sleep quality, the Pittsburgh Sleep Quality Index (PSQI) was used. The quality of sleep decreases with increasing Pittsburgh index score. The calculated dietary quality scores include DASH Index, Healthy Nutrition Index (HEI) and Diet Inflammation Index (DII). RESULTS: The results of this study after adjusting for confounding showed a significant positive relationship between DASH diet score and sleep duration (p <0.001). There was a significant negative relationship between HEI score and total score of PSQI (P = 0.003). Also, HEI score had a significant positive relationship with sleep duration in the unmodified and modified models (p <0.001), and a significant negative relationship was seen in unadjusted and modified model between DII score and sleep duration (p <0.001). CONCLUSION: It can be concluded that with increasing the diet quality in employees, the sleep quality also increases. This was the first study in south of Iran that examined the quality of sleep and diet of employees and the result of this study can affect the general health and improve the quality of foods consumed by employees.

In silico prediction of T-cell and B-cell epitopes of human papillomavirus type 16 L1 protein.

Human papillomavirus type 16 (HPV-16) is one of the most important cause of developing cervical cancer. Therefore, effective epitope-based vaccine design for HPV-16 would be of major medical benefit. The aim of our study was to identify B- and T-cell epitopes of HPV-16 L1 protein. In this study, the HPV-16 L1 gene was isolated from HPV recovered from five vaginal swab samples using specific primers and finally sequenced. The ExPASy translate tool (http://web.expasy.org/translate/) was used to convert nucleotide sequence into amino acid sequence. Bioinformatic analysis was employed to predict suitable B- and T-cell epitopes and immunogenicity, allergenicity, and toxicity of predicted epitopes were then evaluated. Afterward, the selected T-cell epitopes were docked using Molegro Virtual Docker software. The two epitopes 207 AMDFTTLQA215 and 200 MVDTGFGAM208 have showed a very strong binding affinity to HLA-A0201 and HLA-B3501 molecules, respectively. Outcome of B-cell epitope prediction showed that epitope 475 KAKPKFTLGKRK ATPTTSSTSTTAKRKK502 contained overlapped epitope, which might be the epitope associated with the production of neutralizing antibody response. Based on this finding, the predicted B- and T-cell epitopes are promising targets for epitope-based vaccine development against HPV-16. Further in vivo and in vitro experiments are needed to confirm our findings.

Association between deficient levels of circulating vitamin D, dietary intake of vitamin D, calcium and retinol, and risk of colorectal cancer in an Iranian population: A case control study.

AIM: We aimed to assess the association between deficient levels of circulating vitamin D, dietary intake of vitamin D, calcium and retinol, and risk of colorectal cancer in an Iranian population. METHODS: In this retrospective case-control study that was conducted between 2012 and 2015, 278 first incident colorectal cancer cases (colon cancer = 103; rectal cancer = 175), and 278 sex and age matched healthy controls (HCs) were recruited. Serum 25(OH)D, dietary vitamin D, and calcium intake were assessed. Logistic regression was used to estimate the odds ratio (OR) between studied factors and colorectal cancer. Estimates of OR were calculated according to both bivariate analyses based on the matching factors and multivariate analyses, with additional adjustment for potential confounders. RESULTS: A strong inverse linear dose-response association was seen between serum 25(OH)D and colorectal cancer (P for trend = .002). In comparison to serum 25(OH)D more than 40 nmol/L, lower serum concentrations were significantly associated with an increased OR of colorectal cancer. When analyzing anatomical subsites separately, lower circulating 25(OH)D was associated with higher OR for both colon and rectum cancers. Dietary vitamin D and calcium intake were not associated with colorectal cancer. Interaction analysis between serum 25(OH)D and the amount of calcium intake demonstrated that the lowest level of both factors was associated with an increased OR of colorectal cancer. The highest OR of colorectal cancer that was associated with lowest circulating 25(OH)D was stronger at the highest retinol intakes. CONCLUSION: This study demonstrated an inverse strong association between 25(OH)D concentration and colorectal cancer in an Iranian population.

Parechovirus and enteroviruses among young infants with sepsis in Iran.

BACKGROUND AND OBJECTIVES: Human parechoviruses (HPeV) and Human enteroviruses (EV) frequently cause a sepsis-like illness in young infants (younger than three months). Therefore, this study was conducted to determine the frequency of HPeV and EV among the young infants with clinical signs and symptoms of sepsis in Ahvaz city, Iran. MATERIALS AND METHODS: The blood specimens were collected from 100 (younger than 90 days hospitalized infants) including 54 (56.25%) males and 46 (43.75%) females with clinical signs and symptoms of sepsis-like disease. The RNA was extracted and tested for detection of VP1 region of HPeV and 5 UTR (Untranslated Region) of EV by RT-PCR. The sequences of positive of HPeV were further analyzed to determine HPeV genotyping. RESULTS: 5/100 (5%) of patients including 2/46 (2%) females and 3/54 (3%) males tested positive for HPeV (P=0.85). The analysis of 5 positive VP1 region of HPeV revealed the genotype 1. The analysis of sequencing and phylogenetic tree revealed that the isolated HPeVs were genotype 1. While 38/100 (38%) specimens including 16 (16%) females and 22 (22%) males were tested positive for EV (P=0.68). CONCLUSION: The frequency of HPeV genotype 1 was 5% among the young infants with sepsis. While frequency of EV was 38% among the young infants with sepsis. This study showed HPeV genotype 1 and EV are dominant in this region.

Maternal dietary pattern in early pregnancy is associated with gestational weight gain and hyperglycemia: A cohort study in South West of Iran.

BACKGROUND AND AIMS: Maternal dietary pattern could influence on fetal health outcome. Thus, this study was conducted to evaluate the relationship between maternal dietary pattern and Gestational Weight Gain (GWG) in each trimester and hyperglycemia amongst Arab pregnant women in south-west of Iran. METHODS: This longitudinally study was performed in urban healthcare centers of south-west of Iran. Among 610 candidates, 488 pregnant women were included in the final analysis. Consequently, two diet patterns were determined by principal component analysis and the association between GWG and blood glucose level was determined using quartile regression. Using generalized linear model, a model was adjusted for pre-pregnancy BMI, maternal age, income, and education levels. RESULTS: Two dietary patterns were identified as follows: "high fat -fast food" and "vegetable-fruits & protein" pattern. High adherence to "high fat -fast food" pattern was associated with higher GWG and hyperglycemia in 3rd trimester (adjusted ß: 0.029 95%CI 0.012; 0.049 P = 0.001) (adjusted ß: 0.029 95%CI 0.012; 0.049 P = 0.001) respectively. High tendency to "vegetable-fruits & protein" pattern was inversely associated with development of hyperglycemia in 3rd trimester. Higher SES level was associated with low adherence to "high fat-fast food" pattern. CONCLUSION: Findings of the study revealed that, higher adherence to high -fat diet is related to excessive GWG and hyperglycemia in late pregnancy.

New folate receptor targeted nano liposomes for delivery of 5-fluorouracil to cancer cells: Strong implication for enhanced potency and safety.

We previously showed that folate liposomes of 5FU made from Dipalmitoylphosphatidylcholine (DPPC) induced cell death in HT-29 and HeLa cells more potently than bulk 5FU. Also, a primary 5FU liposomal formulation with phosphatidyl choline (PC) exhibited higher cytotoxicity in murine colon cancer cells. In the present study, optimization of 5FU PC liposome, mechanism of cell death induction in human cancer cell lines and its safety along with other assays have been employed for targeted PC liposomes of 5FU. Liposomes were prepared using thin layer method and optimization of preparation was assessed using central composite design (CCD) of response surface methodology (RSM). Folic acid (FA) was employed as the targeting ligand. Morphology of 5FU loaded liposomes and changes in their thermal behavior were assessed by transmission electron microscopy (TEM) and differential scanning calorimetry (DSC), respectively. In vitro cytotoxicity was explored using MTT assay in HT-29, Caco-2, HeLa and MCF-7 cell lines. Cytotoxicity mechanism of the targeted delivery system was searched through the evaluation of reactive oxygen species (ROS) overproduction, mitochondrial membrane potential (∆Ψm), the release of cytochrome c, the activity of caspase 3/7 and apoptosis and necrosis rate. Liposomes were spherical in shape and 5FU was successfully encapsulated into liposomes rather in an amorphous state. Our interesting results showed that in HT-29 cells targeted liposomes triggered the mitochondrial apoptotic pathway by decreasing the mitochondrial membrane potential, releasing of cytochrome c and promoting the substantial activity of caspase 3/7. In HeLa cells, however, targeted liposomes particularly activated necrosis pathway through the overproduction of ROS. Folate-liposomal 5FU showed significantly higher antitumor efficiency compared to free drug. The results of this study offer new prospects for cancer therapy with reducing systemic drug exposure and associated toxicities.

Relationship between environmental Fungi and changes in lung function indices of new referral allergic patients in Ahvaz city under normal and dust conditions.

BACKGROUND: Aim of this study was to determine whether any specific fungal spores could be responsible for changes observed in lung function indices. MATERIALS AND METHODS: 1042 new allergic patients were selected from July 2017 to May 2018 in Ahvaz City, Iran. Fungal samples were collected in normal and dusty condition within 5 and 2 min, respectively. Sampling was repeated once every 6 days and also in the dusty days. RESULTS: Average numbers of fungi colony were 639.86 and 836.44 CFU m-3 under normal and dusty conditions, respectively. Most common fungi in Ahwaz City air were Cladosporium sp., Penicillium sp., Aspergillus Niger, Aspergillus Flavus and Alternaria sp.. Highest fungal mean concentrations, 392 and 480 CFU m-3, were related to Cladosporium sp. under normal and dust conditions, respectively. Average total numbers of colony fungal were 614, 483, 1082, 424 CFU m-3 and 856, 701, 1418, 418 CFU m-3 during the spring, summer, autumn, and winter under normal and dusty conditions, respectively. Patients were evaluated by measured lung function parameters of FEV1 (L), FEV1 (%pred), FVC (L), FVC (%pred), and FEV1/FVC ratio with mean values of 1.85, 58.32, 2.63, 68.18, and 69.43, respectively. CONCLUSION: Increases in mean total spores of fungi in spring were accompanied by decreases in FEV1/FVC ratio. Enhanced spores of Cladosporium sp. in spring led to reduced FEV1/FVC ratio. Increase the spores of Curvularia sp. in summer decreased by FEF25-75%. The augmented spores of Drechslera sp. in summer were associated with declined FEV1 and FEV1/FVC ratio. Enhanced fungal spores of Rhizopus sp. in spring resulted in lowered FEV1, FEV1/FVC ratio, and FEF25-75%.

Echovirus 30 and coxsackievirus A9 infection among young neonates with sepsis in Iran.

BACKGROUND AND OBJECTIVES: Human enteroviruses (EV) are the most common causes of neonatal sepsis-like disease. The frequencies of EV including coxsackievirus A, coxsackievirus B and Echovirus serotypes have been studied in young infants (younger than three months) with sepsis. So far, the role of enteroviruses among neonates with sepsis was not determined in Ahvaz, Iran. Therefore, this study was aimed to evaluate the frequency of EV among hospitalized young infants with clinical signs and symptoms of sepsis in Ahvaz. MATERIALS AND METHODS: Blood specimens from 128 neonates (younger than 90 days), including 56 (43.75%) girls and 72 (56.25%) boys, were collected from hospitalized neonates with clinical signs and symptoms of sepsis-like symptoms. All blood samples were negative for bacterial culture. RNA was extracted from all sera and tested for detection of 5'UTR (Untranslated Region) of the EV by RT-PCR. To determine specific strains of EV, positive 5'UTR samples were further tested for detection of the VP1 region of EV by RT-PCR. RESULTS: Overall, 50/128 (39.06%) specimens, including 24 (48%) girls and 26 (52%) boys, were positive for EV. 21/50 (42%) specimens were positive for the VP1 region. Randomly, 8 positive VP1 were selected and sequenced. Analysis of sequencing data showed 7/21 (33.33%) samples were positive for Echovirus 30 and 1/21 (4.76%) samples were positive for CVA9. CONCLUSION: The results of this survey indicate high prevalence of 39.06% of EV among young neonates with sepsis. A high prevalence of 33.3% Echoviruses 30 and a low rate of 4.76% coxsackievirus A9 infection has been observed in neonatal patients with viral sepsis. This outbreak is probably one of the first Enterovirus outbreaks to be reported in Ahvaz, Iran. The results of this survey will help to minimize unneeded use of antimicrobial drugs and reduce unnecessary hospitalization.

Assessing Reliability and Validity of an Instrument for Measuring Resilience Safety Culture in Sociotechnical Systems.

BACKGROUND: Safety culture, acting as the oil necessary in an efficient safety management system, has its own weaknesses in the current conceptualization and utilization in practice. As a new approach, resilience safety culture (RSC) has been proposed to reduce these weaknesses and improve safety culture; however, it requires a valid and reliable instrument to be measured. This study aimed at evaluating the reliability and validity of such an instrument in measuring the RSC in sociotechnical systems. METHODS: The researchers designed an instrument based on resilience engineering principles and safety culture as the first instrument to measure the RSC. The RSC instrument was distributed among 354 staff members from 12 units of an anonymous petrochemical plant through hand delivery. Content validity, confirmatory, and exploratory factor analysis were used to examine the construct validity, and Cronbach alpha and test-retest were employed to examine the reliability of the instrument. RESULTS: The results of the content validity index and content validity ratio were calculated as 0.97 and 0.83, respectively. The explanatory factor analysis showed 14 factors with 68.29% total variance and 0.88 Kaiser-Meyer-Olkin index. The results were also confirmed with confirmatory factor analysis (relative Chi-square = 2453.49, Root Mean Square Error of Approximation = 0.04). The reliability of the RSC instrument, as measured by internal consistency, was found to be satisfactory (Cronbach α = 0.94). The results of test-retest reliability was r = 0.85, p < 0.001. CONCLUSION: The results of the study suggest that the measure shows acceptable validity and reliability.

A novel 5-Fluorouracil targeted delivery to colon cancer using folic acid conjugated liposomes.

The aim of this study was to develop and characterize 5-Fluorouracil (5FU) containing targeted liposomes in order to enhance the efficacy and safety of the drug. Folic acid (FA) was used as a targeting ligand. The in vitro cytotoxicity of formulation against HT-29, Caco-2, CT26, HeLa and MCF-7 cell lines was evaluated using MTT assay. Mechanism of cell death induced by targeted liposomes was further investigated via the production of reactive oxygen species (ROS), change in mitochondrial membrane potential (ΔΨm), release of cytochrome c and activity of caspase 3/7. The in vivo tumor inhibition study was also performed after administration of drug and targeted 5FU liposome. The encapsulation efficiency (EE%) of the optimized formulation was 39.71%. Particle size of liposomes was around 174 nm and the nanoparticles were found to be spherical in shape. Differential Scanning Calorimetry (DSC) results indicated that the drug remained in an amorphous state in liposomes. According to the MTT results, targeted liposomes exhibited higher cytotoxicity than 5FU and liposomal 5FU. Targeted liposomes were found to trigger necrosis in HT-29 cells; while, in HeLa cells, targeted liposomes activated apoptotic pathway by collapse of ΔΨm, increased activity of cytochrome c as well as caspases activity. in vivo results showed that targeted liposomes reduced tumor volume significantly in comparison with 5FU (169.00 mm3 tumor volume vs 326.40 mm3). From these findings, it can be concluded that folic acid targeted liposomes may provide a new platform for selective delivery of drugs to cancer cells.

Effects of coating layer and release medium on release profile from coated capsules with Eudragit FS 30D: an in vitro and in vivo study.

The aim of the present research was to evaluate the impact of coating layers on release profile from enteric coated dosage forms. Capsules were coated with Eudragit FS 30D using dipping method. The drug profile was evaluated in both phosphate buffer and Hank's solutions. Utilization X-ray imaging, gastrointestinal transmission of enteric coated capsules was traced in rats. According to the results, no release of the drug was found at pH 1.2, and the extent of release drug in pH 6.8 medium was decreased by adding the coating layers. The results indicated single-layer coated capsules in phosphate buffer were significantly higher than that in Hank's solution. However, no significant difference was observed from capsules with three coating layers in two different dissolution media. X-ray imaging showed that enteric coated capsules were intact in the stomach and in the small intestine, while disintegrated in the colon.

Folic acid-modified liposomal drug delivery strategy for tumor targeting of 5-fluorouracil.

The aim of this study was to develop a liposomal formulation to selectively target cancer cells. Liposomes were prepared using thin layer method and folic acid (FA) was applied for targeted delivery of 5FU to cancer cells. Liposomes prepared were characterized for encapsulation efficiency (EE%), morphology and their particle size. Cellular uptake, cytotoxicity study and ROS production were evaluated using CT26 cell line. Hemolysis test was performed on rat red blood cells (RBCs). Moreover, the efficacy of targeted liposomes were investigated by in vivo antitumor activity and tissue toxicities were studied by histological examination. The EE% and average particle size of liposomes were 67.88±1.84% and 114.00±4.58nm, respectively. TEM image revealed that liposomes were spherical in shape. Targeted liposomes showed higher cellular uptake, lower IC50 (12.02µM compared to 39.81µM for liposomal 5FU and 39.81µM for free 5FU) and higher ROS production than free drug (62,271.28 vs 2369.55 fluorescence intensity) on cancer cells. Results of hemolysis assay confirmed the blood biocompatibility of the liposomes. Moreover, folate targeted liposomes showed better tumor inhibition than free drug (88.75mm3 tumor volume vs 210.00mm3) and no tissue abnormalities were found in histological examination. It can be concluded that folate targeted liposomes provide an effective and safe strategy for colon cancer targeted chemotherapy.

Transferrin targeted liposomal 5-fluorouracil induced apoptosis via mitochondria signaling pathway in cancer cells.

The purpose of this study was to prepare transferrin (Tf) targeted liposomal 5-Fluorouracil (5FU) to improve the safety and efficacy of the drug. Liposomes were prepared using thin layer method. Morphology of liposomes was characterized by transmission electron microscopy (TEM) and their particle size was also determined. The in vitro cytotoxicity was investigated via MTT assay on HT-29 (as cancer cell) and fibroblast (as normal cell). Moreover, cytotoxicity mechanism of targeted liposomes was determined through the production of reactive oxygen species (ROS), mitochondrial membrane potential (∆Ψm) and release of cytochrome c. Results showed that encapsulation efficiency (EE%) was 58.66±0.58 and average size of liposomes was 107nm. Also, nano-particles were spherical as shown by TEM. MTT assay on HT-29 cells revealed the higher cytotoxic activity of targeted liposomes in comparison to free drug and non-targeted liposome. In contrast, comparing with cancer cells, targeted liposomes had no cytotoxic effect on normal cells. In addition, targeted liposomes induced apoptosis through activation of mitochondrial apoptosis pathways, as evidenced by decreased mitochondrial membrane potential and release of cytochrome c. Results of the study indicated that targeted liposomes would provide a potential strategy to treat colon cancer by inducing apoptosis via mitochondria signaling pathway with reducing dose of the drug and resulting fewer side-effects.