Current trends and future prospects of drug repositioning in gastrointestinal oncology.

Gastrointestinal (GI) cancers comprise a significant number of cancer cases worldwide and contribute to a high percentage of cancer-related deaths. To improve survival rates of GI cancer patients, it is important to find and implement more effective therapeutic strategies with better prognoses and fewer side effects. The development of new drugs can be a lengthy and expensive process, often involving clinical trials that may fail in the early stages. One strategy to address these challenges is drug repurposing (DR). Drug repurposing is a developmental strategy that involves using existing drugs approved for other diseases and leveraging their safety and pharmacological data to explore their potential use in treating different diseases. In this paper, we outline the existing therapeutic strategies and challenges associated with GI cancers and explore DR as a promising alternative approach. We have presented an extensive review of different DR methodologies, research efforts and examples of repurposed drugs within various GI cancer types, such as colorectal, pancreatic and liver cancers. Our aim is to provide a comprehensive overview of employing the DR approach in GI cancers to inform future research endeavors and clinical trials in this field.

Determining frequency and pattern of infections associated with diabetes based educational hospitals in Ahvaz city; Iran.

BACKGROUND: Diabetes mellitus is a metabolic disease known as one of the most common illness in the world. It is believed that diabetic patients are at high risk of varied infections than non-diabetics. The aim of this study was to determine the frequency and pattern of infections in diabetic patients admitted to the internal wards of educational hospitals of Ahvaz Jundishapur University of Medical Sciences. METHODS: This descriptive cross-sectional study was performed on 700 diabetic patients from January 2014 to December 2015 in internal wards (general, endocrine, gastroenterology, lung, nephrology, cardiology, neurology and infectious diseases) of educational hospitals affiliated to Ahvaz JundishapurUniversity of Medical Sciences. Data includeddemographic information, type of diabetes treatment, duration of diabetes mellitus, final diagnosis, and blood sugar on admission that were analyzed statistically. RESULTS: Out of 700 patients, 374 (53.4%) women and 326 (46.6%) men were entered into this study. The number of non-infectious and infectious patients were 506 (72.3%) and 194 (27.7%). The mean of age,duration of diabetes, and glucose were 62.34 ±â€¯14.38 years, 11.11 ±â€¯7.18 years, and 271.98 ±â€¯90 (mg/dl) in patients with infectious diseases respectively. The most common infectious illnesses were diabetic foot infections (32.5%), pneumonia (18%), soft tissue abscess(13.9%), and urinary tract infections (11.3%). CONCLUSION: Infectious diseases are one of the most common factorsto hospitalize diabetic patients (27.7%), most of whom had diabetic foot infections, pneumonia, and soft tissue abscess.

Evaluation of ELAM-1 expression alteration in endometriosis.

BACKGROUND: Endometriosis is a commonly-encountered gynecological disease characterized by the presence of endometrial glandular and stromal cells outside of the uterus. Several studies have been conducted on endometriosis, however its molecular mechanism and pathogenesis are still not completely clear. The role of ELAM-1 gene in mediating the adhesion of tumor cells to endothelial cells by binding to ELAM-1 ligands expressed by eosinophils, neutrophils, monocytes, natural killer cell effectors, T lymphocyte cells, and cancer (progenitor/stem) cells is well studied. Our hypothesis proposes that the alteration in ELAM-1 mRNA level is a significant point in successful transplantation deregulations of effective migration genes, which may be related to endometrial proliferative disorders such as endometriosis. METHODS: In this study, real time-PCR, Western blotting and immunohistochemistry have been used in order to determine the expression pattern of ELAM-1 gene in 22 patients. For the validation study, a control group of 8 healthy women was recruited. Comparison of the prognostic accuracy of ELAM-1 with other clinical and pathological risk factors were analyzed by logistic regression. RESULTS: The endometriosis tissues from women aged 33±7 years (mean ± SEM) were assessed. The results showed that the ELAM-1 mRNA expression is significantly higher in patients group compare control group (P=0.0001). Moreover, in the samples of stages III and IV, ELAM-1 gene has expressed more (P<0.001). ELAM-1 immunostaining expressed positive staining in the patients group. ELAM-1 protein expression level was correlated directly with American Fertility Society Score and depicted no correlation with age. CONCLUSIONS: According to our results, ELAM-1 upregulation may promote disorder in adhesion, and migration of the cells leading to the endometriosis disorder.

Human unrestricted somatic stem cells loaded in nanofibrous PCL scaffold and their healing effect on skin defects.

Unrestricted somatic stem cells (USSCs) loaded in nanofibrous polycaprolactone (PCL) scaffolds can be used for skin regeneration when grafted onto full-thickness skin defects of rats. Nanofibrous PCL scaffolds were designed by the electrospinning method and crosslinked with laminin protein. Afterwards, the scaffolds were evaluated by scanning electron microscopy, and physical and mechanical assays. In this study, nanofibrous PCL scaffolds loaded with USSCs were grafted onto the skin defects. The wounds were subsequently investigated 21 days after grafting. Results of mechanical and physical analyses showed good resilience and compliance to movement as a skin graft. In animal models; study samples exhibited the most pronounced effect on wound closure, with statistically significant improvement in wound healing being seen at 21 days post-operatively. Histological examinations of healed wounds from all samples showed a thin epidermis plus recovered skin appendages in the dermal layer for samples with cell. Thus, the graft of nanofibrous PCL scaffolds loaded with USSC showed better results during the healing process of skin defects in rat models.

Dental pulp stem cells differentiation into retinal ganglion-like cells in a three dimensional network.

The loss of retinal ganglion cells (RGCs) in majority of retinal degenerative diseases is the first seen pathological event. A lot of studies aim to discover suitable cell sources to replace lost and damaged RGCs. Among them dental pulp stem cells (DPSCs) have a great potential of differentiating into neuronal lineages as well as RGCs. Moreover, three-dimensional (3D) networks and its distribution for growing and differentiation of stem cells as much as possible mimic to native tissue holds great potential in retinal tissue engineering. In this study, we isolate DPSCs from rat incisors and validate them with flow cytometry. Briefly, we differentiated cells using DMEM/F12 containing FGF2, Shh and 0.5% FBS into retinal ganglion-like cells (RGLCs) in two conditions; 3D state in biocompatible fibrin hydrogel and two-dimensional (2D) or conventional culture in polystyrene plates. Immuncytochemical and gene expression analysis revealed the expression of Pax6, Atoh7 and BRN3B increased in 3D fibrin culture compared to 2D conventional culture. In combination, these data demonstrate that using 3D networks can resemble near natural tissue properties for effective generating RGCs which used to treat neurodegenerative diseases such as glaucoma.

Antimutagenic and anticancer effects of lactic acid bacteria isolated from Tarhana through Ames test and phylogenetic analysis by 16S rDNA.

Deaths due to cancer have been increasing in many countries in recent years. One of the beneficial probiotic properties is potential of antimutagenic and anticancer effects. The aim of this study was to investigate antimutagenic and anticancer effects of 25 strains of lactobacilli spp isolated from Tarhana in vitro conditions and to identify selected strains based on molecular biology. Antimutagenicity and anticarcinogenicity tests were performed based on proposed method of Professor Ames et al. Identification of selected strains was performed based on biochemical and molecular tests. Study of antimutagenic and anticancer effects of 25 different strains led to identification of 4 isolates of Lactobacillus spp. Higher antimutagenic activities against sodium azide were observed in cell suspensions of 4 strains as compared with their supernatants. So the inhibitory percentage of cell suspensions among 4 strains was equal to 60.38% in its highest level. Antimutagenicity of these strains was also increased in the presence of rat S9. Four selected strains were identified based on 16S rDNA sequence. Lactobacillus casei, Lactobacillus plantarum, and Lactobacillus brevis isolated from Tarhana exhibited high antimutagenic and anticancer activity. Of 25 strains of lactobacilli, 4 strains with the highest antimutagenicity effect were chosen as new potential probiotic strains.