The obeticholic acid can positively regulate the cancerous behavior of MCF7 breast cancer cell line.

BACKGROUND: The diagnosis and treatment processes of cancer are among the main challenges of medical science in recent decades. The use of different therapeutic agents is one of the most common methods frequently utilized for cancer treatment. Accumulating evidence points to a potential effect of Obeticholic acid (OCA), a specific ligand for farnesoid X receptor, on the regulation of cancer-associated pathways. In spite of tremendous efforts to introduce OCA into the clinical setting, there is a great deal of uncertainty about its impact on breast cancer treatment. This study was performed to evaluate the effects of OCA on breast cancer. METHODS AND RESULTS: In this experiment, the MCF-7 (Michigan Cancer Foundation-7) cell line was treated with 0.1 µM OCA, and cancerous characteristics of the MCF-7 cell line was evaluated by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2 H-tetrazolium bromide) assay, gelatin zymography, western blot, Real-time PCR, flow cytometry, and ELISA techniques. The results indicated that OCA increased the rate of apoptosis and the expression levels of PPARα (Peroxisome proliferator-activated receptor alpha) and TIMP-1 (tissue inhibitor of metalloproteinase-1) genes in this cell line, while it reduced the mRNA levels of MMP7 (matrix metalloproteinase 7) and Bcl-2 (B-cell lymphoma 2) genes, as well as the protein levels of the active form of AKT (protein kinase B), Erk1/2 (extracellular signal-regulated kinase 1/2) and STAT3 (Signal transducers and activators of transcription-3). Also, OCA decreased the activity of MMP9, while it increased the secretion of VEGF-A (vascular endothelial growth factor-A). CONCLUSIONS: It seems that OCA can exert anti-cancer effects on the MCF-7 cells by reducing growth, proliferation, migration, invasion, and regulation of the expression of genes involved in cancer-associated pathways. However, it should be noted that further studies are warranted to establish this concept, especially the increase of VEGF-A can be considered a challenge for the results of this study.

Association between living in the endemic area and level of knowledge of visceral leishmaniasis.

BACKGROUND: Iran is a country with a high prevalence of visceral leishmaniasis (VL) and seven endemic provinces. In this study, we tried to identify unobserved classes of knowledge among Iranians toward VL and assess the predictors of each latent class. METHODS: This cross-sectional study was conducted among randomly selected participants from endemic and non-endemic areas of VL in Iran in 2020 and 2021. The collected data included demographic characteristics and questions about knowledge, attitude, and practice toward VL. We performed latent class analysis using a procedure for latent class analysis (PROC LCA) in SAS to identify the class membership of knowledge of participants toward VL. RESULTS: Five latent classes were identified: very low (38.9%), low (15.5%), moderate (6.2%), high (14.1%), and very high (25.2%) knowledge about VL. Living in endemic areas significantly increased the odds of belonging to the low (adjusted OR (AOR = 7.23; 95% confidence interval (CI):4.52-11.58), high (AOR = 2.71; 95%CI: 1.73-4.23), and very high (AOR = 8.47; 95%CI: 5.78-12.41) classes compared to the very low class. Also, having academic education increased the odds of membership in the very high class (AOR = 2.36; 95%CI: 1.61-3.47) compared to the very low class. CONCLUSION: This study revealed that more than 50% of the participants fell into the latent classes of very low and low knowledge toward VL. Some educational workshops in the endemic areas could be effective in enhancing knowledge about VL.

Pediatric Phlyctenular Keratoconjunctivitis at a Tertiary Care Center in the United States.

PURPOSE: The aim of this study was to evaluate characteristics and outcomes of pediatric phlyctenulosis at a tertiary care center in the United States. METHODS: A retrospective cohort study of phlyctenulosis diagnosis in patients younger than 18 years was conducted. Demographics, presenting features, treatment regimens, and outcomes were analyzed. RESULTS: Seventy patients (95 eyes) with phlyctenulosis were identified. Fifty-four patients (77.1%) were Hispanic, which was greater than the center's proportion of pediatric patients identifying as Hispanic (53.8%, P < 0.0001). Common comorbidities included adjacent external/lid disease (82.9%), allergic/atopic disease (18.6%), and viral infections (8.6%). Nine patients had tuberculosis testing which was negative in all cases. Five patients had vitamin A testing which revealed deficiency in 1 patient. Treatment regimens were diverse and included varying combinations of topical and systemic medications. Complications included corneal scarring (27.4%), corneal neovascularization (40.0%), amblyopia (16.8%), corneal perforation (3.2%), and severe limbal stem-cell deficiency (1.1%). 26.3% of affected eyes had final visual acuity worse than 20/40. Differences in rates of corneal complications between Hispanic and non-Hispanic patients were not statistically significant, although severe corneal complications including perforation occurred only in the Hispanic group. CONCLUSIONS: This study presents a modern cohort of phlyctenulosis at a tertiary center in the United States and includes a larger proportion of Hispanic patients than expected. Phlyctenulosis carries high corneal morbidity and may frequently result in reduced visual acuity. Similar rates of corneal complications were seen in Hispanic versus non-Hispanic patients, but severe corneal complications were seen only in the Hispanic group.

Evaluating the effect of a mixture of two main conjugated linoleic acid isomers on hepatic steatosis in HepG2 cellular model.

Hepatic steatosis is an early form of non-alcoholic fatty liver disease (NAFLD), caused by abnormal fat deposition in the hepatocytes. Conjugated linoleic acid (CLA) is a group of positional and geometric dienoic isomers of linoleic acid that attract significant attention because of its beneficial effects on chronic diseases such as cancer, obesity, and metabolic syndrome. This study examined the influence of a mixture of two main CLA isomers (CLA-mix) on lipid accumulation and lipid metabolism-related genes using HepG2 cells treated with palmitic acid (PA) as an in vitro model for hepatic steatosis. Methods and Results: HepG2 cells were treated for 24 h: control (BSA), model (BSA + PA), and treated groups (BSA-PA + non-toxic concentrations of CLA-mix). Intracellular lipid deposition, triglyceride (TG), total cholesterol (TC) and gene expression were measured by Oil-Red O staining, colorimetric assay kits and real-time PCR, respectively. CLA-mix at high concentrations had significantly decreased intracellular total lipid and TG deposition compared to the model group. However, none of the CLA-mix concentrations had a significant effect on the intracellular TC level. CLA-mix significantly increased the expression of some genes mainly regulated by PPARα but did not alter the expression of lipogenesis-related genes. Conclusions: These results demonstrate that high concentrations of CLA-mix protect against hepatic steatosis and play a role in regulating fatty acid oxidation and bile excretion through the PPARα pathway. It is suggested that the effect of different ratios of two main CLA isomers on the amount and ratio of bile compounds be investigated in future studies.

Typical features of cutaneous leishmaniasis in the Ilam province, Iran.

Since Cutaneous leishmaniasis is a problematic parasitic infection in the west of Iran, this study was carried out to clarify the epidemiological aspects of Cl. Our database includes all Cl cases with detailed information during 2014-2018 in Ilam province, west of Iran. Patients referred to health and clinical centers in our study areas then health providers and laboratory technicians took smears to detect leishmania parasites under light microscope. SPSS24 software used for analyzing data by the Chi square test. Mehran and Dehloran districts were alone accounted for 50% of all reported cases. ≥ 36 age group was dominant cases also housekeepers were at the top of categories in case of occupation. Hand and leg entangled with this infection more than other organs. Moreover, most cases observed in the winter season, and lesions were 1-3 cm in size. Apart from decreasing Cl cases in our study location compared to 2014, building debris around the urban area should be cleaned up concerning standards of hygiene in each phase to keep rodents away. Additionally, citizens at the land border of Iran-Iraq should protect themselves from sand fly biting at least by insect repellent at peak travel times.

Integrated Bioinformatics Analysis of mRNAs and miRNAs Identified Potential Biomarkers of Oral Squamous Cell Carcinoma.

Background: Oral cancer is a frequently encountered neoplasm of the head and neck region, being the eighth most common type of human malignancy worldwide. Despite improvement in its control, morbidity and mortality, rates have improved little in the past decades. The present investigations about gene interaction and pathways still could not clear the appearance and development of oral squamous cell carcinoma (OSCC), completely. The aim of this study is to investigate the key genes and microRNAs interaction in OSCC. Materials and Methods: The microarray datasets GSE13601 and GSE98463, including mRNA and miRNA profiles, were extracted from the GEO database and were analyzed using GEO2R. Functional and pathway enrichment analyses were performed by using the DAVID database. The protein-protein interaction (PPI) network was constructed and analyzed using STRING database and Cytoscape software, respectively. Finally, miRDB was applied to predict the targets of the differentially expressed miRNAs (DEMs). Results: Totally, 97 differentially expressed genes (DEGs) were found in OSCC, including 66 up-regulated and 31 down-regulated genes. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses showed that up-regulated genes were significantly enriched in movement of cell or subcellular component, cell adhesion, biological adhesion, cellular localization, apoptotic signaling pathway, while the downregulated genes were enriched in muscle system process and oxidation-reduction process. From the PPI network, the top 10 nodes with the highest degree were detected as hub genes. In addition, 18 DEMs were screened, which included 7 up-regulated and 11 down-regulated miRNAs. STAT1 was potentially targeted by three miRNAs, including has-miR- 6825-5P, has-miR-4495, and has-miR-5580-3P. Conclusion: The roles of DEMs such as hsa-mir-5580-3p in OSCC through interactions with DEGs CD44, ACLY, ACTR3, STAT1, LAMC2 and YWHAZ may offer a suitable candidate biomarker pattern for diagnosis, prognosis and treatment processes in OSCC.

Epidemiological survey of tularemia in Ilam Province, west of Iran.

BACKGROUND: Francisella tularensis is the causative agent of tularemia in humans and a large number of animal species. Considering recent evidence of the circulation of this bacterium in different parts of Iran, especially in the western provinces, the aim of current study was to determine the tularemia seroprevalence in the human population living in Ilam Province. METHODS: In 2015, 360 serum samples were collected from five groups of people: ranchers (n = 112), farmers (n = 79), butchers and slaughterhouse workers (n = 61), Nature Conservation Officers (n = 34), and referents of medical diagnostic laboratories (n = 74). These samples were tested for the presence of anti- F. tularensis IgG antibodies using the ELISA method. RESULTS: According to the ELISA manufacturer cutoffs, we found that 10 (2.78%) and 9 (2.5%) sera, respectively, were positive or borderline for F. tularensis IgG antibodies. The highest tularemia seroprevalence was observed among farmers (7.59%). CONCLUSIONS: Our results strongly support the circulation of tularemia in Ilam Province. Because no human tularemia case has been reported so far in this province, we recommend specific education programs to increase knowledge of local health care professionals about this important zoonotic disease.

Hydro-thermal priming enhance seed germination capacity and seedling growth in sugar beet.

Seed priming improves seed performance in many crop species. In this study, the influence of hydrothermal priming on seed parameters of sugar beet is investigated in both laboratory and field conditions. In the laboratory, the treatments consist of a combination of cultivars (Arya and Shokoofa), hydro-priming at two temperatures (10 and 15 °C) for 6, 10, 14, 18, 22 hours. Germination traits and seedling growth were measured for determination of optimum hydro-thermal priming. Also, the protein pattern in the optimum hydro-thermal priming treatments and unprimed seeds were compared by electrophoresis. In the field experiment, the percentage and rate of emergence of primed and unprimed seeds were measured. Results showed that hydro-thermal priming had a positive effect on final germination percentage, mean germination time and uniformity of germination. Optimum hydro-thermal priming time and the temperature were 6 and 10 hours at 15 °C for Shokoofa and Arya cultivars respectively. Hydro-thermal priming increased the seed emergence percentage in the field by 15%. There was no significant difference in protein pattern between primed and unprimed seeds. In general, hydro-thermal priming not only increases sugar beet seed germination in the laboratory but also has a more positive effect on the emergence in the field condition.

Cutaneous leishmaniasis prevalence and morbidity based on environmental factors in Ilam, Iran: Spatial analysis and land use regression models.

The aim of this study was to investigate the impact of the environmental factors on cutaneous leishmaniasis (CL) prevalence and morbidity in Ilam province, western Iran, as a known endemic area for this disease. Accurate locations of 3237 CL patients diagnosed from 2013 to 2015, their demographic information, and data of 17 potentially predictive environmental variables (PPEVs) were prepared to be used in Geographic Information System (GIS) and Land-Use Regression (LUR) analysis. The prevalence, risk, and predictive risk maps were provided using Inverse Distance Weighting (IDW) model in GIS software. Regression analysis was used to determine how environmental variables affect on CL prevalence. All maps and regression models were developed based on the annual and three-year average of the CL prevalence. The results showed that there was statistically significant relationship (P value≤0.05) between CL prevalence and 11 (64%) PPEVs which were elevation, population, rainfall, temperature, urban land use, poorland, dry farming, inceptisol and aridisol soils, and forest and irrigated lands. The highest probability of the CL prevalence was predicted in the west of the study area and frontier with Iraq. An inverse relationship was found between CL prevalence and environmental factors, including elevation, covering soil, rainfall, agricultural irrigation, and elevation while this relation was positive for temperature, urban land use, and population density. Environmental factors were found to be an important predictive variables for CL prevalence and should be considered in management strategies for CL control.

Persistent staining of lattice lines after intraoperative trypan blue use in patients with lattice corneal dystrophy.

PURPOSE: The aim of this study was to report the persistent staining of corneal lattice lines resulting from the intraoperative use of trypan blue. METHODS: This is a case series. RESULTS: Four patients with lattice corneal dystrophy (LCD) who underwent either deep anterior lamellar keratoplasty or cataract extraction with intraoperative trypan blue use demonstrated persistent, postoperative trypan staining of lattice lines on slit-lamp examination out to final follow-up (range, 176 to 541 days postoperatively). CONCLUSIONS: This case series demonstrates the previously unreported finding that intraoperative trypan blue stains corneal lattice lines in LCD. Trypan blue staining, localized in previous laboratory studies to amyloid deposits, seems to persist for months or longer and may be permanent in human tissue. Although the staining was not visually significant, animal models suggest a stimulatory effect on progression of amyloidosis. Clinicians should be aware of the potential for permanent corneal staining and possible disease progression with the use of intraoperative trypan blue in patients with LCD.

Association of cys 311 ser polymorphism of paraoxonase-2 gene with the risk of coronary artery disease.

BACKGROUND: Recently another member of the paraoxonase gene family designated paraoxonase-2 has been identified. Paraoxonase-2 has antioxidant properties similar to paraoxonase-1 and paraoxonase-3. However, in contrast to paraoxonase-1 and paraoxonase-3, paraoxonase-2 is not associated with high-density lipoprotein and may only exert its antioxidant function at the cellular level. METHODS: We assessed the frequency and genotype distribution of cys 311 ser paraoxonase-2 polymorphism in 300 subjects (>40 years old) with angiographic documentation of coronary artery disease (150 patients with >50% stenosis served as cases and 150 individuals with <20% stenosis served as controls) to determine the possible association between this mutation and susceptibility for coronary artery disease. The paraoxonase-2 genotypes were determined by polymerase chain reaction and DdeI restriction enzyme digestion. RESULTS: The cases (coronary artery disease positive patients) showed significant differences in the distribution of cys 311 ser paraoxonase-2 genotypes as compared with the controls (coronary artery disease negative subjects, P=0.015). The analysis of paraoxonase-2 genotypes distribution showed higher percentage of CC genotype among coronary artery disease positive compared with coronary artery disease negative (P=0.008). After controlling for other risk factors, the cys 311 ser polymorphism had not correlation with age, body mass index, gender, smoking, diabetes, level of high-density lipoprotein, low-density lipoprotein, triglyceride, and total cholesterol. CONCLUSION: Our data indicate a major effect of the paraoxonase-2 polymorphism on coronary artery disease risk in patients referred to Shariati Hospital in Tehran.