Identification and structural characterization of deleterious non-synonymous single nucleotide polymorphisms in the human SKP2 gene.

In SCF (Skp, Cullin, F-box) ubiquitin-protein ligase complexes, S-phase kinase 2 (SKP2) is one of the major players of F-box family, that is responsible for the degradation of several important cell regulators and tumor suppressor proteins. Despite of having significant evidence for the role of SKP2 on tumorgenesis, there is a lack of available data regarding the effect of non-synonymous polymorphisms. In this communication, the structural and functional consequences of non-synonymous single nucleotide polymorphisms (nsSNPs) of SKP2 have been reported by employing various computational approaches and molecular dynamics simulation.

Metal based donepezil analogues designed to inhibit human acetylcholinesterase for Alzheimer's disease.

Among neurodegenerative disorders, Alzheimer's disease (AD) is one of the most common disorders showing slow progressive cognitive decline. Targeting acetylcholinesterase (AChE) is one of the major strategies for AD therapeutics, as cholinergic pathways in the cerebral cortex and basal forebrain are compromised. Herein, we report the design of some copper and other metal based donepezil derivatives, employing density functional theory (DFT).

Nanotoxicity of different sizes of graphene (G) and graphene oxide (GO) in vitro and in vivo.

Graphene family nanomaterials (GFNs) have attracted significant attention due to their unique characteristics and applications in the fields of biomedicine and nanotechnology. However, previous studies highlighted the in vitro and in vivo toxicity of GFNs with size and oxidation state differences are still elusive. Therefore, we prepared graphene (G) and graphene oxide (GO) of three different sizes (S-small, M-medium, and L-large), and characterized them using multiple surface-sensitive analytical techniques.

Immunoinformatic and systems biology approaches to predict and validate peptide vaccines against Epstein-Barr virus (EBV).

Epstein-Barr virus (EBV), also known as human herpesvirus 4 (HHV-4), is a member of the Herpesviridae family and causes infectious mononucleosis, Burkitt's lymphoma, and nasopharyngeal carcinoma. Even in the United States of America, the situation is alarming, as EBV affects 95% of the young population between 35 and 40 years of age. In this study, both linear and conformational B-cell epitopes as well as cytotoxic T-lymphocyte (CTL) epitopes were predicted by using the ElliPro and NetCTL.

Comparison Between Uses Of Contraceptive Methods In LHW Covered And LHW Uncovered Areasxxx.

Background: Family planning is of great importance in population dynamics as unregulated fertility negatively affects the economic stabilization of the country. Family planning is considered an effective way for the improvement of child and maternal health and reduces the maternal and perinatal morality. Total contraceptive prevalence rate (CPR) in Pakistan is 29% even of the fact that 97% Pakistani women know only one method of contraception.

Molecular docking and dynamics of Nickel-Schiff base complexes for inhibiting β-lactamase of .

In recent years, multidrug-resistance has become a primary concern in the treatment and management of tuberculosis, an infectious disease caused by . In this context, searching new anti-tuberculosis agents particularly targeting the β-lactamase (BlaC) is reported to be promising as this enzyme is one of the key player in the development of multidrug resistance. This study reports the design of some Nickel (Ni) based tetradentate NO Schiff bases, employing density functional theory.

Helix-Switch Enables C99 Dimer Transition between the Multiple Conformations.

C99 is the immediate precursor of amyloid-β (Aβ) and therefore is a central intermediate in the pathway that is believed to result in Alzheimer's disease (AD). Recent studies have shown that C99 dimerization changes the Aβ ratio, but the mechanism remains unclear. Previous studies of the C99 dimer have produced controversial structure models.

Radiological and clinical outcomes in patients undergoing anterior cervical discectomy and fusion: Comparing titanium and PEEK (polyetheretherketone) cages.

Objectives: To study clinical and radiological outcomes in patients who had undergone the procedure of anterior cervical discectomy and fusion with titanium or PEEK (polyetheretherketone) cages for cervical disc prolapse.

Methods: This is a retrospective/non-randomized study which was conducted at the Combined Military Hospital Peshawar. Study interval was four years from 1st October, 2010 to 31st September, 2014.

Pyrazinamide resistance and mutations L19R, R140H, and E144K in Pyrazinamidase of Mycobacterium tuberculosis.

Pyrazinamide (PZA) is an important component of first-line antituberculosis drugs activated by Mycobacterium tuberculosis pyrazinamidase (PZase) into its active form pyrazinoic acid. Mutations in the pncA gene have been recognized as the major cause of PZA resistance. We detected some novel mutations, Leucine19Arginine (L19R), Arginine140Histidine (R140H), and Glutamic acid144 Lysine (E144K), in the pncA gene of PZA-resistant isolates in our wet lab PZA drug susceptibility testing and sequencing.

Insights into the Mechanisms of the Pyrazinamide Resistance of Three Pyrazinamidase Mutants N11K, P69T, and D126N.

In an effort to discover the mechanism of resistance offered by Mycobacterium tuberculosis (Mtb) toward the pyrazinamide (PZA) drug, an extensive molecular dynamics strategy was employed. PZA is a first-line prodrug that effectively cuts therapy time by 33% (from 9 to 6 months). Pyrazinamidase enzyme (PZase), encoded by the pncA gene, is responsible for the activation of prodrug PZA into pyrazinoic acid (POA).

Cytotoxicity and molecular docking studies on phytosterols isolated from Polygonum hydropiper L.

Based on our previous studies on cytotoxic potentials of Polygonum hydropiper L, two steroidal compounds beta-sitosterol and stigmasterol were isolated from the most active fraction and were subjected to cell lines cytotoxicity. Isolated compounds were tested against HeLa, MCF-7 and NIH/3T3 cell lines following MTT assay. Furthermore, the compounds were also docked against tyrosine kinase enzyme to predict the binding mode of phytosterols in the active sites of the enzyme.

Insight into novel clinical mutants of RpsA-S324F, E325K, and G341R of associated with pyrazinamide resistance.

Pyrazinamide (PZA) is an important component of first-line anti-tuberculosis drugs which is converted into active form, pyrazinoic acid (POA), by (MTB) gene encoded, pyrazinamidase (PZase). Mutations in are detected in >70% of PZA resistant isolates but, noticeably, not in all. In this study, we selected 18 PZA-resistant but wild type (pncA) MTB isolates.

Prospecting and Structural Insight into the Binding of Novel Plant-Derived Molecules of Leea indica as Inhibitors of BACE1.

Background: Alzheimer disease (AD) can be considered as the most common age related neurodegenerative disorder and also an important cause of death in elderly patients. A number of studies showed the correlation of this disease pathology with BACE1 inhibitor and it is also evident that BACE1 inhibitor can function as a very potent strategy in treating AD.

Methods: In this present study, we aimed to prospect for novel plant-derived BACE1 inhibitors from Leea indica and to realise structural basis of their interactions and mechanisms using combined molecular docking and molecular dynamics based approaches.

Cancer Immunoinformatics: A Promising Era in the Development of Peptide Vaccines for Human Papillomavirus-induced Cervical Cancer.

Cancer immunoinformatics have led to new directions towards vaccine design from predicted potential epitope candidates, which are able to stimulate the correct cellular or humoral immune responses. They were employed to accomplish an advanced vaccine design through reverse vaccinology by replacing the whole organisms. In this review, computational tools play an essential role in evaluating multiple proteomes to identify and select the potential targeted epitopes or combinations of distinct epitopes, so that candidates may afford a rationale design competent for obtaining suitable cytotoxic T lymphocytes (CTL) or B cell-mediated immune responses.

The systematic modeling studies and free energy calculations of the phenazine compounds as anti-tuberculosis agents.

Phenazine compounds have good activity against (MTB). Based on the reported activities that were obtained in MTB H37Rv, a three-dimensional quantitative structure-activity relationship (3D-QSAR) model was built to design novel compounds against MTB. A fivefold cross-validation method and external validation were used to analyze the accuracy of forecasting.

Structural-dynamic insights into the cytotoxin-associated gene A (CagA) and its abrogation to interact with the tumor suppressor protein ASPP2 using decoy peptides.

() is one of the most extensively studied Gram-negative bacteria due to its implication in gastric cancer. The oncogenicity of is associated with cytotoxin-associated gene A (CagA), which is injected into epithelial cells lining the stomach. Both the - and -termini of CagA are involved in the interaction with several host proteins, thereby disrupting vital cellular functions, such as cell adhesion, cell cycle, intracellular signal transduction, and cytoskeletal structure.

Optic nerve Schwannoma: Neurofibromatosus Type-1? A case report.

Optic nerve Schwannoma is a very rare tumour described in literature. The rarity of this tumour is due to the fact that the optic nerve is myelinated by oligodendrocytes. We present a case of an ancient optic nerve schwannoma in a 16 year old girl who presented to the clinic with right sided proptosis and bilateral loss of vision.

Lipid compositional changes and oxidation status of ultra-high temperature treated Milk.

Background: Milk fat is one of the complex fat and most sensitive biochemical compounds towards auto-oxidation. To enhance the shelf life, milk is subjected to Ultra-high Temperature (UHT) treatment followed by aseptic packaging. During the storage, several chemical and biochemical changes take place in lipid fraction of UHT milk.

A comprehensive review on current status, mechanism, and possible sources of arsenic contamination in groundwater: a global perspective with prominence of Pakistan scenario.

Arsenic(As)-mediated contamination of groundwater resources in different parts of the world is a consequence of natural or anthropogenic sources, leading to adverse effects on the environment and human health. Millions of people from different countries are unfortunately consuming groundwater contaminated with alarming levels of As. Exposure to the high concentration of As for an extended period of time can cause devastating effects on human health such as skin lesions, cardiac disorders, discolouration and cancer.

Mechanistic toxicity of DEHP at environmentally relevant concentrations (ERCs) and ecological risk assessment in the Three Gorges Reservoir Area, China.

Di-(2-ethylhexyl) phthalate (DEHP) associated in vitro/vivo toxicity at current environmentally relevant concentration (ERC) with attendant ecological risks in the Three Gorges Reservoir Area (TGRA) is still elusive. Responding to this challenge, a novel integrated study based on analytical and biological assays was designed to elucidate the underlying mechanisms for toxicity of DEHP and its ecological risks at ERC. In this study, GC-MS analysis showed that the highest environmental concentration of DEHP in the TGRA surface water was nearly double that of WHO and USEPA standards.

An experience with ventriculoperitoneal shunting at keen's point for hydrocephalus.

Objective: This study was conducted to assess outcomes in patients with hydrocephalus who underwent ventriculoperitoneal shunting at Keen's point.

Methods: This retrospective study was conducted in Combined Military Hospital (CMH) Peshawar. Time frame was four years from January 2011 to January 2015.

New toxicogenetic insights and ranking of the selected pharmaceuticals belong to the three different classes: A toxicity estimation to confirmation approach.

Tetracycline hydrochloride (TH), indomethacin (IM), and bezafibrate (BF) belong to the three different important classes of pharmaceuticals, which are well known for their toxicity and environmental concerns. However, studies are still elusive to highlight the mechanistic toxicity of these pharmaceuticals and rank them using both, the toxicity prediction and confirmation approaches. Therefore, we employed the next generation toxicity testing in 21st century (TOX21) tools and estimated the in vitro/vivo toxic endpoints of mentioned pharmaceuticals, and then confirmed them using in vitro/vivo assays.

Inherited Bleeding Disorders-Experience of a Not-for-Profit Organization in Pakistan.

Patient registry is a powerful tool for planning health care and setting groundwork for research. This survey reports a detailed registry of inherited bleeding disorders (IBD) and their management at a not-for-profit organization in a developing country to form the basis for planning development and research. We reviewed medical records of patients with IBD from 8 hemophilia treatment centers of Fatimid Foundation located in various cities.

Transcriptomic response and perturbation of toxicity pathways in zebrafish larvae after exposure to graphene quantum dots (GQDs).

Graphene quantum dots (GQDs) are widely used for biomedical applications. Previously, the low-level toxicity of GQDs in vivo and in vitro has been elucidated, but the underlying molecular mechanisms remained largely unknown. Here, we employed the Illumina high-throughput RNA-sequencing to explore the whole-transcriptome profiling of zebrafish larvae after exposure to GQDs.