Thyroid hormone dependent gene expression

The presented work is destined to review the advances that had been made to study the role of thyroid hormone and thyroid hormone nuclear receptors in regulating the gene expression. Triiodothyronine (T3) and tetraiodothyronine (thyroxine or T4) are most important thyroid hormones. The thyroid hormones bind to their specific nuclear hormone receptors, as ligand, and play important role in gene expression and transcriptional gene regulation in human and higher animals. Thyroid hormone receptors form heterodimers by making combination with retinoid X receptors. The capability of heterodimerization of thyroid hormones generates novel complexes which allow altered specificity and higher affinity for DNA-receptor binding. Thyroid hormone receptors work as ligand activated transcription factor and play with transcriptional gene expression process. The consensus structural features of thyroid hormone receptors are N-terminal regulatory domain that contains activation function, the domain for strong gene expression and the domain for binding to DNA. The structures for individual domains have been extensively and reviewed through several latest and successful techniques.

Resistance of polio to its eradication in Pakistan

<p>Abstract</p> <p>Background</p> <p>This study is based on EPI (Expanded Program on Immunization) immunization surveys and surveillance of polio, its challenges in immunization and the way forward to overcome these challenges.</p> <p>Methods</p> <p>Several Government documents, survey reports and unpublished program documents were studied and online search was made to find information on EPI Pakistan. SPSS 16 and Microsoft Excel 2007 were used for the statistical analysis.</p> <p>Results</p> <p>Immunization against polio is higher in urban areas as compared to rural areas. Marked variation in vaccination has been observed in different provinces of Pakistan in the last decade. Secondly 10-20% of the children who have received their first dose of trivalent polio vaccine were deprived of their 2^ndand 3^rddose because of poor performance of EPI and Lack of information about immunization.</p> <p>Conclusion</p> <p>In spite of numerous successes, such as the addition of new vaccines and raising immunization to over 100% in some areas, EPI is still struggling to reach its polio eradication goals. Inadequate service delivery, lack of information about immunization and limited number of vaccinators were found to be the key reason for poor performance of immunization and for large number of cases reported each year due to the deficiency of second and third booster dose.</p

A situational analysis of HIV and AIDS in Pakistan

HIV (Human immunodeficiency virus) transmission has been reduced by protected sex and screening of blood products and other body fluids in the developed countries. It has been reported that Pakistan is at high risk of HIV/AIDS infection but presently the prevalence rate is considerably low. The number of reported cases of HIV/AIDS in Pakistan has been continuously increasing since 1987. By 2010 the total number of registered cases has reached to 6000 and this figure is on the rise with the passage of time. Some serious strategies must be implemented to control this deadly disease

Role of MicroRNA in Endometrial Carcinoma

Endometrial carcinoma (EC) is a hall mark of gynecological malignancies that usually affects women above the age 50. It is one of the major causes of mortality in females with ever increasing prevalence and the mortality rate is 1.7 to 2.4 per 100000 and each year 10000 death occur due to ECs. MiRNAs regulate the expression of different proto-oncogenes and signaling pathways that are directly or indirectly involved in the development of cancer. Different miRNAs i.e. (miRNA-449, miRNA 370, miRNA-424, and miRNA-152) which gets up or down regulated during endometrial cancer are the potential biomarkers for early diagnosis of EC. Targeting this relationship between the miRNA and signaling pathways may help in the development of new treatment in endometrial cancer. In current study, we reviewed literature from PubMed using miRNA and endometrial cancer as keywords and outlined the synthesis of potent miRNA and role of different miRNAs involved in ECs. The study revealed different sub types of miRNA played crucial role in the development of cancer by up and down regulation of different metabolic pathways. Many evidences have supported that miRNAs play role in control and regulation of different pathways leading to cancer and targeting these pathways may bring changes in the diagnosis as well as in treatment of EC

A brief review on molecular, genetic and imaging techniques for HCV fibrosis evaluation

<p>Abstract</p> <p>Background</p> <p>Chronic HCV is one of the major causes of morbidity and mortality in the present day world. The assessment of disease progression not only provides useful information for diagnosis and therapeutic supervision judgment but also for monitoring disease. Different invasive and non invasive methods are applied to diagnose the disease from initial to end stage (mild fibrosis to cirrhosis). Although, liver biopsy is still considered as gold standard to identify liver histological stages, an assessment of the disease development based on non-invasive clinical findings is also emerging and this may replace the need of biopsy in near future. This review gives brief insight on non-invasive methods currently available for predicting liver fibrosis in HCV with their current pros and cons to make easier for a clinician to choose better marker to assess liver fibrosis in HCV infected patients.</p> <p>Methods</p> <p>More than 200 studies regarding invasive and noninvasive markers available for HCV liver disease diagnosis were thoroughly reviewed. We examined year wise results of these markers based on their sensitivity, specificity, PPV, NPV and AUROCs.</p> <p>Results</p> <p>We found that in all non-invasive serum markers for HCV, FibroTest, Forn's Index, Fibrometer and HepaScore have high five-year predictive value but with low AUROCs (0.60~0.85) and are not comparable to liver biopsy (AUROC = 0.97). Even though from its beginning, Fibroscan is proved to be best with high AUROCs (> 0.90) in all studies, no single noninvasive marker is able to differentiate all fibrosis stages from end stage cirrhosis. Meanwhile, specific genetic markers may not only discriminate fibrotic and cirrhotic liver but also differentiate individual fibrosis stages.</p> <p>Conclusions</p> <p>There is a need of marker which accurately determines the stage based on simplest routine laboratory test. Genetic marker in combination of imaging technique may be the better non invasive diagnostic method in future.</p

NS4A protein as a marker of HCV history suggests that different HCV genotypes originally evolved from genotype 1b

<p>Abstract</p> <p>Background</p> <p>The 9.6 kb long RNA genome of Hepatitis C virus (HCV) is under the control of RNA dependent RNA polymerase, an error-prone enzyme, for its transcription and replication. A high rate of mutation has been found to be associated with RNA viruses like HCV. Based on genetic variability, HCV has been classified into 6 different major genotypes and 11 different subtypes. However this classification system does not provide significant information about the origin of the virus, primarily due to high mutation rate at nucleotide level. HCV genome codes for a single polyprotein of about 3011 amino acids which is processed into structural and non-structural proteins inside host cell by viral and cellular proteases.</p> <p>Results</p> <p>We have identified a conserved NS4A protein sequence for HCV genotype 3a reported from four different continents of the world i.e. Europe, America, Australia and Asia. We investigated 346 sequences and compared amino acid composition of NS4A protein of different HCV genotypes through Multiple Sequence Alignment and observed amino acid substitutions C₂₂, V₂₉, V₃₀, V₃₈, Q₄₆and Q₄₇in NS4A protein of genotype 1b. Furthermore, we observed C₂₂and V₃₀as more consistent members of NS4A protein of genotype 1a. Similarly Q₄₆and Q₄₇in genotype 5, V₂₉, V₃₀, Q₄₆and Q₄₇in genotype 4, C₂₂, Q₄₆and Q₄₇in genotype 6, C₂₂, V₃₈, Q₄₆and Q₄₇in genotype 3 and C₂₂in genotype 2 as more consistent members of NS4A protein of these genotypes. So the different amino acids that were introduced as substitutions in NS4A protein of genotype 1 subtype 1b have been retained as consistent members of the NS4A protein of other known genotypes.</p> <p>Conclusion</p> <p>These observations indicate that NS4A protein of different HCV genotypes originally evolved from NS4A protein of genotype 1 subtype 1b, which in turn indicate that HCV genotype 1 subtype 1b established itself earlier in human population and all other known genotypes evolved later as a result of mutations in HCV genotype 1b. These results were further confirmed through phylogenetic analysis by constructing phylogenetic tree using NS4A protein as a phylogenetic marker.</p

A comparison of four fibrosis indexes in chronic HCV: Development of new fibrosis-cirrhosis index (FCI)

<p>Abstract</p> <p>Background</p> <p>Hepatitis C can lead to liver fibrosis and cirrhosis. We compared readily available non-invasive fibrosis indexes for the fibrosis progression discrimination to find a better combination of existing non-invasive markers.</p> <p>Methods</p> <p>We studied 157 HCV infected patients who underwent liver biopsy. In order to differentiate HCV fibrosis progression, readily available AAR, APRI, FI and FIB-4 serum indexes were tested in the patients. We derived a new fibrosis-cirrhosis index (FCI) comprised of ALP, bilirubin, serum albumin and platelet count. FCI = [(ALP × Bilirubin) / (Albumin × Platelet count)].</p> <p>Results</p> <p>Already established serum indexes AAR, APRI, FI and FIB-4 were able to stage liver fibrosis with correlation coefficient indexes 0.130, 0.444, 0.578 and 0.494, respectively. Our new fibrosis cirrhosis index FCI significantly correlated with the histological fibrosis stages F0-F1, F2-F3 and F4 (r = 0.818, p < 0.05) with AUROCs 0.932 and 0.996, respectively. The sensitivity and PPV of FCI at a cutoff value < 0.130 for predicting fibrosis stage F0-F1 was 81% and 82%, respectively with AUROC 0.932. Corresponding value of FCI at a cutoff value ≥1.25 for the prediction of cirrhosis was 86% and 100%.</p> <p>Conclusions</p> <p>The fibrosis-cirrhosis index (FCI) accurately predicted fibrosis stages in HCV infected patients and seems more efficient than frequently used serum indexes.</p

Exosomes in Cancer: Diagnostic and Therapeutic Applications

Small extracellular vesicles called exosomes are produced by cells and contain a range of biomolecules, including proteins, lipids, and nucleic acids. Exosomes have been implicated in the development and spread of cancer, and recent studies have shown that their contents may be exploited as biomarkers for early detection and ongoing surveillance of the disease. In this review article, we summarize the current knowledge on exosomes as biomarkers of cancer. We discuss the various methods used for exosome isolation and characterization, as well as the different types of biomolecules found within exosomes that are relevant for cancer diagnosis and prognosis. We also highlight recent studies that have demonstrated the utility of exosomal biomarkers in different types of cancer, such as lung cancer, breast cancer, and pancreatic cancer. Overall, exosomes show great promise as noninvasive biomarkers for cancer detection and monitoring. Exosomes have the ability to transform cancer diagnostic and therapeutic paradigms, providing promise for more efficient and individualized. This review seeks to serve as an inspiration for new ideas and research in the never-ending fight against cancer. Moreover, further studies are needed to validate their clinical utility and establish standardized protocols for their isolation and analysis. With continued research and development, exosomal biomarkers have the potential to revolutionize cancer diagnosis and treatment

Exosomes as Biomarker of Cancer

ABSTRACT Rapid advances in medicine and biotechnology resulted in the development of non-invasive diagnostic and prognostic biomarkers enabling convenient and accurate detection. Exosomes has recently emerged as non-invasive biomarker for a number of diseases including cancer. Exosomes are the small endosome originated membranous vesicles secreted in a number of biological fluids such as serum, saliva, urine, ascites, cerebrospinal fluid, etc. Exosomes contain microRNA proteins and mRNA which can be used as disease specific biomarkers. Here we reviewed recent advancement in the field of exosomes as diagnostic biomarker for cancer along with a brief overview of their biogenesis, function and isolation

A Winning New Combination? Toward Clinical Application in Oncology

Immunotherapy has substantial attention in oncology due to the success of CTLA-4 and PD-1 inhibitors in the treatment of melanoma, lung cancer, head and neck cancer, renal cell carcinoma, and Hodgkin’s lymphoma. A deeper understanding of interaction of tumor with its environment and the immune system provides best guide for oncology research. Recent studies in oncology have explained how a tumor alters antigen presentation, avoids detection, and activation of the host immune system to live and develop. Understanding the connections between the tumor and the immune system has resulted in several innovative therapy options. The extensive field of gene therapy has provided a number of cutting-edge medicines that are expected to play an important role in lowering cancer-related mortality. This article explains the history, important breakthroughs, and future prospects for three separate gene therapy treatment modalities: immunotherapy, oncolytic virotherapy, and gene transfer. Immunotherapies have completely changed how cancer is treated, especially for individuals whose condition was previously thought to be incurable. Examples include ACT (adoptive cell therapy) and ICB (immune checkpoint blockade). This review article will discuss the relationship between the immune response to cancer and the mechanisms of immunotherapy resistance. It will cover combination drugs authorized by the US Food and Drug Administration and provide a thorough overview of how these drugs are doing clinically right now. Cytokines, vaccines, and other soluble immunoregulatory agents, innate immune modifiers, ACT, virotherapy, and other treatment modalities will all be covered in detail