A pan-cancer analysis of pituitary tumor-transforming 3, pseudogene.

BACKGROUND: Although evidence regarding pituitary tumor-transforming 3, pseudogene (PTTG3P) involvement in human cancers has been acquired via human and animal model-based molecular studies, there is a lack of pan-cancer analysis of this gene in human tumors. METHODS: Tumor-causing effects of PTTG3P in 24 human tumors were explored using The Cancer Genome Atlas (TCGA) datasets from different bioinformatics databases and applying in silico tools such as The University of ALabama at Birmingham CANcer (UALCAN), Human Protein Atlas (HPA), Kaplan Meier (KM) plotter, cBioPortal, Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), Cytoscape, Database for Annotation, Visualization, and Integrated Discovery (DAVID), Tumor IMmune Estimation Resource (TIMER), and Comparative Toxicogenomics Database (CTD). Then, via in vitro experiments, including RNA sequencing (RNA-seq) and targeted bisulfite sequencing (bisulfite-seq), expression and promoter methylation levels of PTTG3P were verified in cell lines. RESULTS: The PTTG3P expression was overexpressed across 23 malignancies and its overexpression was further found significantly effecting the overall survival (OS) durations of the esophageal carcinoma (ESCA) and head and neck cancer (HNSC) patients. This important information helps us to understand that PTTG3P plays a significant role in the development and progression of ESCA and HNSC. As for PTTG3P functional mechanisms, this gene along with its other binding partners was significantly concentrated in "Oocyte meiosis", "Cell cycle", "Ubiquitin mediated proteolysis", and "Progesterone-mediated oocyte maturation". Moreover, ESCA and HNSC tissues having the higher expression of PTTG3P were found to have lower promoter methylation levels of PTTG3P and higher CD8+ T immune cells level. Additionally, PTTG3P expression-regulatory drugs were also explored in the current manuscript for designing appropriate treatment strategies for ESCA and HNSC with respect to PTTG3P expression. CONCLUSION: Our pan-cancer based findings provided a comprehensive account of the oncogenic role and utilization of PTTG3P as a novel molecular biomarker of ESCA and HNSC.

Association of Serum Albumin, Globulin, and Transferrin Levels in Children of Poorly Managed Celiac Disease.

Background: Celiac disease (CD) is an autoimmune genetic disorder in which gluten protein causes inflammation of the intestinal enterocytes. CD diagnosis in most cases is delayed or mistreated due to its varied clinical features. We aimed to evaluate the protein profile imbalance in different CD groups of children, which could help aid in the diagnosis and proper management of the disease. Methodology. This was a cross-sectional study with a nonrandom purposive sampling technique. All samples were taken from tertiary care hospitals of Hyderabad, Pakistan. In total, there were 175 children (age 3-15 years) divided into five equal groups (n = 35), namely, group A (control), group B (celiac diagnosed), group C (celiac-like symptoms), group D (celiac with type 1 diabetes mellitus), and group E (type 1 diabetes mellitus only). Clinical symptoms and laboratory parameters were analyzed among all the groups. Sera proteins, albumin, globulins, and transferrin levels were evaluated and compared with healthy individuals. Results: The albumin in serum of celiac groups B and C was 3.0 g/dl and 2.8 g/dl, respectively. While in diabetic patients with CD, it is 2.7 g/dl. The globulin levels were raised among all the celiac groups with typical GIT symptoms. The highest transferrin was observed in group B, celiac patients with severe anemia. Patients were not on GFD, hence had no or less recovery and had chronic symptoms of celiac. Conclusion: The misdiagnosis and poor management of celiac leads to chronic villous atrophy with imbalance in metabolic profile. Serum analysis of albumin, globulins, and transferrin may help in the diagnosis and proper management of the disease to recover the celiac symptoms.

Integrating Spatial Modelling and Space-Time Pattern Mining Analytics for Vector Disease-Related Health Perspectives: A Case of Dengue Fever in Pakistan.

The spatial-temporal assessment of vector diseases is imperative to design effective action plans and establish preventive strategies. Therefore, such assessments have potential public health planning-related implications. In this context, we here propose an integrated spatial disease evaluation (I-SpaDE) framework. The I-SpaDE integrates various techniques such as the Kernel Density Estimation, the Optimized Hot Spot Analysis, space-time assessment and prediction, and the Geographically Weighted Regression (GWR). It makes it possible to systematically assess the disease concentrations, patterns/trends, clustering, prediction dynamics, and spatially varying relationships between disease and different associated factors. To demonstrate the applicability and effectiveness of the I-SpaDE, we apply it in the second largest city of Pakistan, namely Lahore, using Dengue Fever (DF) during 2007-2016 as an example vector disease. The most significant clustering is evident during the years 2007-2008, 2010-2011, 2013, and 2016. Mostly, the clusters are found within the city's central functional area. The prediction analysis shows an inclination of DF distribution from less to more urbanized areas. The results from the GWR show that among various socio-ecological factors, the temperature is the most significantly associated with the DF followed by vegetation and built-up area. While the results are important to understand the DF situation in the study area and have useful implications for public health planning, the proposed framework is flexible, replicable, and robust to be utilized in other similar regions, particularly in developing countries in the tropics and sub-tropics.

EMT imparts cancer stemness and plasticity: new perspectives and therapeutic potential.

Epithelial-to-mesenchymal transition (EMT) is a fundamental cellular phenomenon that plays an intrinsic role in development, tissue repair, and cancer progression. EMT is tightly regulated by transcription factors that alter gene expression to promote epithelial to mesenchymal phenotype. EMT is also regulated by a diverse array of cytokines and growth factors whose activities are deregulated during malignancy. EMT enables tumor cells to exist in various intermediate states along the epithelial-mesenchymal phenotypic axis that transit from cancer stem cells (CSCs) to circulating tumor cells (CTCs). Recent studies have revealed the importance of CSCs in tumor promotion, invasion and metastasis. The relapsed tumors encompass CSCs which are resistant to radiotherapy and chemotherapy. In this review, we have summarized our current understanding of the molecular mechanisms that regulate EMT induced CSC phenotype. We have highlighted studies implicating the function of TGF-�, Wnt, and Notch regulated non-coding RNAs in driving EMT promoting CSC self-renewal. Finally, we discuss how the EMT and CSCs cause drug resistance with the hope to overcome such resistance as a possible approach for cancer treatment.