Viruses as tools in gene therapy, vaccine development, and cancer treatment.

Using viruses to our advantage has been a huge leap for humanity. Their ability to mediate horizontal gene transfer has made them useful tools for gene therapy, vaccine development, and cancer treatment. Adenoviruses, adeno-associated viruses, retroviruses, lentiviruses, alphaviruses, and herpesviruses are a few of the most common candidates for use as therapeutic agents or efficient gene delivery systems. Efforts are being made to improve and perfect viral-vector-based therapies to overcome potential or reported drawbacks. Some preclinical trials of viral vector vaccines have yielded positive results, indicating their potential as prophylactic or therapeutic vaccine candidates. Utilization of the oncolytic activity of viruses is the future of cancer therapy, as patients will then be free from the harmful effects of chemo- or radiotherapy. This review discusses in vitro and in vivo studies showing the brilliant therapeutic potential of viruses.

Comparative molecular docking analysis for analyzing the inhibitory effect of Anakinra and Ustekinumab against IL17F.

Interleukin 17 F is a member of IL-17 cytokine family with a 50% structural homology to IL-17A and plays a significant role either alone or in combination with IL-17A towards inflammation in Rheumatoid arthritis (RA). A growing number of drugs targeting IL-17 pathway are being tested against population specific disease markers. The major objective of this research was to investigate the anti-inflammatory effect of Anakinra (an IL-1 R1 inhibitor) and Ustekinumab (an IL-12 and IL-23 inhibitor) by targeting IL17F. The three dimensional structures of IL17F was taken from PDB while structures of drugs were taken from PubChem database. Docking was performed using MOE and Schrodinger ligand docking software and binding energies, including s-score using London-dG fitness function and glide score using glide internal energy function, between drug and targets were compared. Furthermore, Protein-Drug complex were subjected to 150 ns Molecular Dynamics (MD) Simulations using Schrodinger's Desmond Module. Docking and MD simulation results suggest anakinra as a more potent IL17F inhibitor and forming a more structurally stable complex.Communicated by Ramaswamy H. Sarma.

Assessment of Health-Related Quality of Life, Medication Adherence, and Prevalence of Depression in Kidney Failure Patients.

BACKGROUND: Kidney failure is a global health problem with a worldwide mean prevalence rate of 13.4%. Kidney failure remains symptomless during most of the early stages until symptoms appear in the advanced stages. Kidney failure is associated with a decrease in health-related quality of life (HRQOL), deterioration in physical and mental health, and an increased risk of cardiovascular morbidity and mortality. This study aimed to evaluate the factors associated with decreased HRQOL and other factors affecting the overall health of patients. Another objective was to measure how medication adherence and depression could affect the overall HRQOL in patients with kidney failure. METHODOLOGY: The study used a prospective follow-up mix methodology approach with six-month follow-ups of patients. The participants included in the study population were those with chronic kidney disease grade 4 and kidney failure. Pre-validated and translated questionnaires (Kidney Disease Quality of Life-Short Form, Hamilton Depression Rating Scale Urdu Version, and Morisky Lewis Greens Adherence Scale) and assessment tools were used to collect data. RESULTS: This study recruited 314 patients after an initial assessment based on inclusion criteria. The mean age of the study population was 54.64 ± 15.33 years. There was a 47.6% male and a 52.4% female population. Hypertension and diabetes mellitus remained the most predominant comorbid condition, affecting 64.2% and 74.6% of the population, respectively. The study suggested a significant (p < 0.05) deterioration in the mental health composite score with worsening laboratory variables, particularly hematological and iron studies. Demographic variables significantly impact medication adherence. HRQOL was found to be deteriorating with a significant impact on mental health compared to physical health. CONCLUSIONS: Patients on maintenance dialysis for kidney failure have a significant burden of physical and mental symptoms, depression, and low HRQOL. Given the substantial and well-known declines in physical and psychological well-being among kidney failure patients receiving hemodialysis, the findings of this research imply that these areas related to health should receive special attention in the growing and expanding population of kidney failure patients.

Recent progress in the utilization of biosynthesized polyhydroxyalkanoates for biomedical applications - Review.

PHAs (polyhydroxyalkanoates) have emerged as biodegradable plastics more strongly in the 20th century. A wide range of bacterial species along with fungi, plants, oilseed crops and carbon sources have been used extensively to synthesize PHA on large scales. Alteration of PHA monomers in their structures and composition has led to the development of biodegradable and biocompatible polymers with highly specific mechanical properties. This leads to the incorporation of PHA in numerous biomedical applications within the previous decade. PHAs have been fabricated in various forms to perform tissue engineering to repair liver, bone, cartilage, heart tissues, cardiovascular tissues, bone marrow, and to act as drug delivery system and nerve conduits. A large number of animal trials have been carried out to assess the biomedical properties of PHA monomers, which also confirms the high compatibility of PHA family for this field. This review summarizes the synthesis of PHA from different sources, and biosynthetic pathways and biomedical applications of biosynthesized polyhydroxyalkanoates.

Hepatitis delta virus genotype-1 alone cocirculates with hepatitis B virus genotypes A and D in Pakistan.

INTRODUCTION: Hepatitis delta virus (HDV) and hepatitis B virus (HBV) have been identified as major causes of morbidity and mortality in Pakistan because HDV causes infection only in the presence of HBV. Coinfection with both hepatitis viruses can lead to a more severe acute form of disease and to an increased risk of fulminant hepatitis. HDV infection differs in its distribution and severity depending on the geographical distribution, and several genotypes of HDV have been identified so far. OBJECTIVES: The aim of the present study was to establish the HDV and HBV genotypes in chronically infected Pakistani patients and to determine whether there is any correlation between HDV and HBV genotypes. PATIENTS AND METHODS: We studied samples from a total of 46 chronically infected HBV and HDV patients for HBV and HDV genotype analysis out of a total of 75 chronic HBV carriers enrolled. HBV and HDV genotypes were determined using type-specific PCR, followed by sequencing of PCR amplified products. RESULTS: The results of HBV genotyping showed that 33 of 46 (71.7%) patients had genotype D, five (10.9%) had A+D mixed genotypes, whereas eight (17.3) samples were untypable. We could detect only one HDV genotype (HDV-1) prevalent in the Pakistani population. The HDV-1 genotype isolate was associated with HBV genotype D alone or in combination with A (HBV-A+D). CONCLUSION: The present study concludes that HDV/HBV coinfection is very high in the Pakistani population and was previously underestimated. The most prevalent circulating genotypes of HBV and HDV are HDV-1 and HBV-D, respectively, in the studied area. There is no specific interaction between HBV and HDV genotypes as suggested by HDV-1/HBV-D or HDV-1/HBV-A+D coinfection. Coinfection of HDV-1 and HBV-D simply reflects the most frequent genotypes circulating in this specific geographical region of the world.

The role of antepartum transabdominal amnioinfusion in the management of oligohydramnios in pregnancy.

OBJECTIVE: The purpose of this study was to evaluate the role of transabdominal amnioinfusion in the management of oligohydramnios with the view to improving pregnancy outcome. METHODS: The study consisted of a retrospective analysis of 17 pregnant women presenting with oligohydramnios who were treated with amnioinfusion during pregnancy in a period from 2003 to 2006. RESULTS: The mean gestational age at first treatment was 24 weeks. The mean pre-procedure deepest pool of amniotic fluid was 1.8 cm and post-procedure was 3.8 cm. The mean number of infusions was 1.05. The mean first infusion to delivery interval was 31 days. Perinatal mortality was 88% and neonatal mortality was 35%, with only one baby surviving the neonatal period. There were three cases of chorioamnionitis, with one of these cases presenting with premature rupture of the membranes at the time of amnioinfusion. CONCLUSIONS: Transabdominal amnioinfusion is a useful procedure to reduce complications that result from oligohydramnios. Although the results show a high perinatal mortality, it must be borne in mind that most of these pregnancies had multiple fetal abnormalities with an already predicted poor outcome. Importantly, as this procedure increases the latency period, it may be useful in preterm pregnancies where prolonging the duration of the pregnancy may result in better perinatal outcome by improving important factors that influence survival including increased birthweight.