Statins are commonly used to lower the cholesterol level by inhibiting an important enzyme, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA), of the mevalonate pathway. [1]  In addition, statins affect many cellular and biological processes, including cell proliferation and differentiation, apoptosis, antigen presentation and immune responses by inhibiting the prenylation of important proteins, including Ras, Rho and Rab GTPases that are critically important to alter the signaling of important molecules. [2]  As a result of their cholesterol-dependent and -independent activities, statins exhibit pleiotropic effects that include anti-inflammatory, anti-oxidant, immunomodulatory and anti-thrombotic actions. [1] Given the lipid-independent effect of statins in the inflammation and immunomodulation, it is not surprising that statins may alter T cell activation through their prenylation-inhibitory activity. In addition to monocyte/macrophages, T cells and Natural Killer T (NKT) cells also play critical roles in the disease progression of atherosclerosis. The plaques from the symptomatic patients have shown the presence of activated T cells. [3,4]   By virtue of secreting pro-inflammatory cytokines, T cells perpetuate the inflammation and contribute to the further recruitment of the immune cells into the atherosclerotic plaques. [5] MHC class II and CD1d molecules traffic through the endocytic compartments in order to be loaded with proper ligands. It is critical for the antigen-specific activation of CD4+ T cells and NKT cells.[1] Activated CD4+ T cells and NKT cells secrete huge amounts of pro-inflammatory cytokines that aggravate the severity of atherosclerotic inflammation. Simvastatin has been shown to inhibit the T-cell proliferation and cytokine production by impairing MHC class II-mediated antigen presentation. [6] This effect of statin on MHC class II antigen presentation is dependent on its prenylation inhibitory activity. Earlier studies showed that the depletion of the isoprenoid pool by using a specific inhibitor of HMG-CoA resulted in the regulation of T cell migration. [7]  By inhibiting T cell activation, statins can alleviate the inflammation in atherosclerotic plaques through its lipid-independent effect. NKT cells comprise a set of T cells that are mainly activated by the lipid antigens presented by MHC class I-like CD1d molecules. NKT cells play a very important role in host defense against tumors and infectious diseases. [8] On the other hand, NKT cells have also been implicated in the aggravation of atherosclerosis, asthma and other inflammatory diseases. The pro-atherogenic role of NKT cells implies into their ability to secrete a huge amount of pro-inflammatory cytokines. [9] This assumption is supported by the report that the higher level of iNKT cells exacerbated the status of atherosclerosis in obese mice. [10] Furthermore, the presence of NKT cells and CD1d-expressing antigen presenting cells have been detected in the atherosclerotic plaques. [11]  Mitogen-activated protein kinase (MAPK), Protein kinase delta (PKCδ) and JAK/STAT cell signaling pathways regulate the CD1d-mediated antigen presentation by altering their intracellular trafficking through the endocytic compartments. [12]  A small GTPase, Arl8b, has been known to influence the antigen presentation by CD1d by altering the lysosomal trafficking. [13]  We earlier have reported that simvastatin inhibited the CD1d- and MHC class II-mediated antigen presentation. Interestingly, it did not reduce the cholesterol level in the treated cells. [1] It suggested that the effect of statin on CD1d-mediated antigen presentation is dependent on prenylation inhibitory activity of the drug. Moreover, statin-induced inhibition of prenylation altered the trafficking and distribution of CD1d in the endocytic compartments of the treated antigen presenting cells. Overall, these findings clearly indicate that statin-mediated inhibition of prenylation modulates the activation of T cell and  NKT cell resulting in the alleviation of the inflammation in the atherosclerotic plaques. The prenylation inhibitory property of statin may further be exploited in the treatment of diseases where inflammation plays an important role in the pathogenesis of the diseases.

Objectives: The project is based on extensive studies on applied nanoparticles in biology and medicine. This study was primarily designed to investigate the role of magnetic nanoparticles by comparing the absorbance and stabilization of DNA-C, L by the electrophoretic detection. Methods: Fe 3 O 4 magnetic nanoparticles (MNPs) with core/shell structure of silica coatings were synthesized by a chemical coprecipitation method. This work is done at 15 min times with multitimes, that is, 20 numbers and nanoparticles are provided regular with good morphology which was synthesized in 20 nm in size, and its structure was analyzed by tools such as EDX analysis. Next, 20 mg of the magnetic nanoparticles were coated with silica in a heterogeneous solution at 25 μg / ml of the solution of each of the mixed DNAs (ring, linear) in separate containers. Finally, 15 minutes later, DNA was adsorbed on the surface of the nanoparticles. The amount of this adsorption was injected by spectrophotometry (UV-Vis, ith 99% accuracy and optimized by the standard Tris.HCl buffer required to separate DNA from its pure solution (unabsorbed DNA)) and electrophoresis.  Results: The results showed that absorption and diffusion of DNA-C or L at the surface of nanoparticles were 95% and 85%, respectively (i.e., absorbance of DNA-C>DNA-L is) with rate of removing of on MNPs was >99%. Hence, after review, we received that a linkage of electrostatic bonding between nanoparticles and biomolecules was obtained, and the results of the EDX analysis confirmed this study. Conclusion: In this project, nanocomposites containing magnetic nanoparticles were synthesized and their structure was identified by relevant analyzes. It was then used to stabilize the biomolecules, which yielded competitive results between the two types of DNA (linear and cyclic) at 85 and 95% adsorption, respectively.  

Objective: This study was conducted to find out the possible association of Vitamin D receptor, caudal-related homeobox 2 (VDR-Cdx2) polymorphism with cancer in the given study group. Materials and Methods: In this study, 151 subjects (84 cases and 67 controls) were recruited from two local tertiary care hospitals of Karachi, Pakistan, suffering from various cancers including gastric cancer (GC), rectal cancer (RC), colon cancer (CC), and multiple myeloma followed by ethical approval from institutions and informed consent from all the participants. The genotyping of VDR-Cdx2 polymorphism was performed using tetra-primer amplification refractory mutation system-polymerase chain reaction method. The genotypic assortment/distribution in the control and disease groups was according to Hardy-Weinberg’s equilibrium. Results: The genotype frequencies of VDR-Cdx2 polymorphism in cancer patients were observed as: AA 1.2%, AG 32%, and GG 66.8% while in control group as; AA 7.5%, AG 50.7%, and GG was 41.8%. The results unveil that the genotype VDR-Cdx2 was found significantly different in cancer and control group (P < 0.01). The AG and GG genotypes were found to be associated with the cancer (P < 0.05). Therefore, these genotypes may be considered as the risk factors for cancer. However, the frequencies of “A” and “G” alleles were not significantly different between two groups. Conclusion: The observed single-nucleotide polymorphism of VDR-Cdx2 gene may be considered as a risk factor for the cancer in this study group. The AG and GG genotypes established an association with various cancers including GC, RC, CC, and multiple myeloma in Pakistani population. Further investigations examining large data are required to compare the role of VDR-Cdx2 polymorphism in cancer etiology in related population.

Objectives: Dysphagia post stroke represents a substantial health issue. The rates of pneumonia are lesser among those individuals who have passed a dysphagia-screening test. Only few among the existing screening tests meet the required standards; The Timed water swallow test is one among them. The purpose of the study was to establish normative data for the TWST in Indian population. Method : The present study involved 480 typical individuals in the age range of 8 -80.11 years. All the participants performed TWST and indices of volume per swallow, time per swallow and swallow capacity were obtained for the tasks of normal and rapid swallow across age and gender. Results : In the first phase of the study, normative data were obtained and summarized by age and gender. The second phase of the study dealt with additional analyses on measures of reliability and validity. Two way Mixed ANOVA was performed with age and gender as the between group variables, and normal and rapid swallowing as the within group variables. Conclusion: Normative values for the performance of Indian population on TWST was obtained. The results revealed a significant difference for all the three indices of swallow performance across age, gender and type of swallowing. These norms can be used as a screening tool for identifying swallowing dysfunction.

Objective: Acute myeloid leukemia (AML) is a common malignant disorder of hematopoietic progenitor cells that caused by chromosomal translocation and the formation of fusion oncogenes. This study determined the frequencies of fusion genes in Sudanese patients with AML and their clinical impacts. Methods: This study was conducted at Alzaeim Alazhari University, Khartoum, Sudan. A total of 97 patients with AML were recruited in the study from different clinics in Khartoum state. Quantitative real-time polymerase chain reaction was used to determine types of fusion genes. Results: The highest frequency of genetic defects was observed for AML1-ETO fusion gene (57.6%) followed by MLL-AF9 (35.1%) and FUS-ERG (7.2%). No significant differences in blast cells, hemoglobin, total white blood cells, and platelets were found between different gene fusion groups (P > 0.05). In addition, no differences in the frequency of splenomegaly, hepatomegaly and lymphadenopathy were observed between different gene fusion groups (P > 0.05). With respect to French-American-British (FAB) classification, the M2 and M3 were significantly higher in patients with AML1-ETO fusion (86%, P < 0.01) whereas M4-M5 were higher in patients with MLL-AF9 fusion (76.5%, P < 0.01). Conclusions: The study concluded that AML1-ETO and MLL-AF9 fusion genes were predominant in AML Sudanese patients. None of the examined clinical parameters were different between different fusion genes except for FAB stages.

Objectives: The study aimed at detecting the prevailing Hepatitis B Virus (HBV) genotypes and the presence of clinically relevant mutations in the precore/core gene of the HBV DNA, among patients with chronic infection in South-eastern, Nigeria. Methods: A total of 72 participants with chronic HBV infection were enrolled into the study. Plasma samples from those with detectable HBV DNA were subjected to nested Polymerase Chain Reaction amplification using the precore/core specific primers. This resulted to the successful amplification and sequencing of the HBV precore/core region DNA from 16 participants. Mutation analysis on the precore/core region detected the presence of certain HBV precore/core gene mutations. Genotyping was carried out by phylogenetic analysis. Results: The precore region mutation at nucleotide position 1896, which is a G to A change resulting to a nonsense mutation, was detected in 6.25% of the participants. Other HBV precore region mutations that were detected include: G1899A, T1846A, G1862C, G1888A, T1821C, C1826T, A1827C, A1850T, C1858T, precore start codon kozak sequence mutations and some novel core region mutations such as G/A1951T and G1957A. Genotyping revealed the existence of HBV genotype/subgenotype A1 (87.5%) and D (12.5%) among the participants. There was no significant difference in the occurrence of specific precore/core mutations among the HBV/HCV dually infected and HBV mono-infected participants. Conclusion: The data suggests the likelihood of a more severe outcome of hepatitis caused by HBV in South-eastern Nigeria due to the occurrence of a variety of precore/core mutation, which resulted to HBeAg-negative chronic HBV infection among the participants.

Objective: Physical inactivity and unhealthy dietary habits are behavioural risk factors associated with non-communicable diseases. The current study aimed to determine the prevalence of physical activity and dietary habits among adolescents in Saudi Arabia. Methods: A systematic electronic literature search of PubMed, SCOPUS, Web of Science, and BIOSIS was conducted through April 2018 using the following keywords: (physical activity OR physical inactivity OR diet OR dietary habits) AND Saudi Arabia. Extracted data from each study were tabulated, and data were synthesised narratively. Results: Eighteen studies published within 2007-2017 were included in the narrative synthesis. The prevalence of physical activity among adolescents in Saudi Arabia ranged from 4% to 44.5%. Fast foods consumption, skipping breakfast, and low fruit and vegetable consumption were the most reported unhealthy dietary habits.   Conclusion: Our review highlights that physical inactivity and unhealthy dietary habits were high among adolescents in Saudi Arabia. These findings require immediate actions and plans to increase levels of physical activity and healthy dietary habits among Saudi adolescents.  

Objective: The objective of this meta-analysis and systematic review is to analyze the efficacy of physiotherapy interventions in management of lumbar prolapsed intervertebral disc (PIVD). Method: Randomized controlled trials (RCTs) were searched in PubMed and Cochrane Library using related keywords and advanced option, from commencement to January 2019. Quality of researches was assessed by PEDro scoring. Risk of bias and homogeneity were assessed using Cochrane risk of bias tool and I2value, respectively. Meta-analysis of included study was done using “Review manager (Software, version 5.3).” Results: Eleven RCTs were included in this systematic review. Six RCTs were excluded from meta-analysis due to insufficient data availability. Meta-analysis reveals significant decrease in pain (P = 0.001, mean difference (MD) −0.91; 95% confidence interval (CI) −0.35 to −1.48) and disability (P < 0.0001; MD −5.76; 95%CI; −3.18 to −8.34) with moderate heterogeneity (I2=40%; P = 0.17, I2=54%; P = 0.09, respectively). There was non-significant improvement in straight leg raise (SLR), P = 0.07; MD 7.96; 95%CI; −0.59–16.51 with moderate heterogeneity (I2=56%; P = 0.11). Conclusion: Physiotherapy interventions are effective in management of lumbar PIVD. Physiological and biomechanical factors such as correction of the displaced disc, opening of the foramina, increase in intervertebral space, and reduction in herniation size with negative intradiscal pressure may be possible mechanisms.

Pierre-Robin sequence has been known to present with multiple somatic abnormalities. It is known that the syndrome impairs cardiogenesis. However, the reason for this is unknown. Impaired cardiogenesis manifests in the form of various defects such as ventricular septal defect and atrial septal defect but presence of tetralogy of Fallot is very rare.