Valuation of knowledge, attitude, practices of tuberculosis among the health care workers from Islamabad Pakistan.

Background: Tuberculosis (TB) as a foremost infectious disease adds massive burden to morbidity and mortality rate, despite of well-structured TB control programs around the globe. Inappropriate health care management system and poor implementation on standard in relevance to TB, remain some reasons causative to TB prevalence and its rising antimicrobial resistance. Health Care Workers (HCWs) laboring as a part of TB control system, are the vital warriors in achieving the goals of TB End Strategy by 2035.

Potential diagnostic and drug target markers in glioblastoma.

Glioblastoma multiforme (GBM) IDH-wildtype is the most prevalent brain malignancy in adults. However, molecular mechanisms, which leads to GBM have not been completely elucidated. Granulocyte colony-stimulating factor (GCSF), Granulocyte colony-stimulating factor receptor GCSFR, and Signal transducers and activators of transcription 3 (STAT3) have been involved in the occurrence and development of various cancers, but their role in GBM is little known.

Celecoxib Suppresses NF-κB p65 (RelA) and TNFα Expression Signaling in Glioblastoma.

Background: Glioblastoma (GBM) harbors significant genetic heterogeneity, high infiltrative capacity, and patterns of relapse following many therapies. The expression of nuclear factor kappa-B (NF-κB p65 (RelA)) and signaling pathways is constitutively activated in GBM through inflammatory stimulation such as tumor necrosis factor-alpha (TNFα), cell invasion, motility, abnormal physiological stimuli, and inducible chemoresistance. However, the underlying anti-tumor and anti-proliferative mechanisms of NF-κB p65 (RelA) and TNFα are still poorly defined.

REVIEW-The Biological importance of cells secreted Exosomes.

Exosomes are the extracellular vesicles secreted normally by most of the cells, containing important bioactive molecules including lipids, carbohydrates, protein, DNA and RNA resulting in cell to cell communication and many other biological activities. In this review we have focused on different insight onto exosomes to cover its basic mechanism, biogenesis, biomolecules it carries and how they are altering secondary sites. In cancerous cells these tiny bodies are reported to be secreted aberrantly and through paracrine signalling contributes in metastasis.

The role of exosomes derived miRNAs in cancer.

Exosomes are 20-150nm cell secreting nano-bodies that helps in the transportation of various biomolecules, including micro ribonucleic acid (miRNA) in the human body during both normal and diseased conditions. The current review was planned to summarise the role of miRNA carried by circulatory exosomes in cancer. miRNA is responsible for contribution in cancer, regulation of gene expression, interfering in biological pathways, gene silencing or amplification, and also has a role in cancer resistance.

Identification of differentially expressed genes and pathways crosstalk analysis in Rheumatoid and Osteoarthritis using next-generation sequencing and protein-protein networks.

Osteoarthritis occurs when protective cartilage of bones worn out. Similarlty, cartilage damage occurs mainly in the pannus cartilage in rheumatoid arthritis. It is a potentially debilitating condition, affecting women two to three times more often than men.

Isolation and Characterization of Leishmanial Adenine Aminohydrolase as a Drug Target.

Background: Search for new drug targets is becoming imperative these days, given that marketed chemotherapeutic drugs have lost their efficacy against harmful agents because of adaptability to climatic changes and co-evolving vectors to new hosts. In the wake of such a challenge, the prominence of biochemical studies is increasing by way of exploring selective enzymes and investigating their structural and functional properties through biochemical kinetic parameter Km for the application of IC50 using designed drugs. Recently, discovered Adenine Aminohydrolase (EC 3.

SARS-CoV-2 nucleocapsid and Nsp3 binding: an in silico study.

Severe acute respiratory syndrome virus 2 (SARS-CoV-2) belongs to the single-stranded positive-sense RNA family. The virus contains a large genome that encodes four structural proteins, small envelope (E), matrix (M), nucleocapsid phosphoprotein (N), spike (S), and 16 nonstructural proteins (nsp1-16) that together, ensure replication of the virus in the host cell. Among these proteins, the interactions of N and Nsp3 are essential that links the viral genome for processing.

Gibbs Free Energy Calculation of Mutation in PncA and RpsA Associated With Pyrazinamide Resistance.

A central approach for better understanding the forces involved in maintaining protein structures is to investigate the protein folding and thermodynamic properties. The effect of the folding process is often disturbed in mutated states. To explore the dynamic properties behind mutations, molecular dynamic (MD) simulations have been widely performed, especially in unveiling the mechanism of drug failure behind mutation.

Characterization and synthetic biology of lipase from Bacillus amyloliquefaciens strain.

Lipases with high tolerance to temperature play a significant role in industry from food manufacturing to waste management systems. Thus, there is a need to investigate these enzymes from different geographical areas to look out for a more thermo-stable one. Characterization of lipases through experimental approaches is time consuming process and sometimes the results are ambiguous due to errors.

Marine Natural Products and Drug Resistance in Latent Tuberculosis.

Pyrazinamide (PZA) is the only drug for the elimination of latent (MTB) isolates. However, due to the increased number of PZA-resistance, the chances of the success of global TB elimination seems to be more prolonged. Recently, marine natural products (MNPs) as an anti-TB agent have received much attention, where some compounds extracted from marine sponge, Haliclona sp.

Structural dynamics behind variants in pyrazinamidase and pyrazinamide resistance.

Pyrazinamide (PZA) is an important component of first-line anti-tuberculosis (anti-TB) drugs. The anti-TB agent is activated into an active form, pyrazinoic acid (POA), by (MTB) gene encoding pyrazinamidase (PZase). The major cause of PZA-resistance has been associated with mutations in the gene.

Structural and free energy landscape of novel mutations in ribosomal protein S1 (rpsA) associated with pyrazinamide resistance.

Resistance to key first-line drugs is a major hurdle to achieve the global end tuberculosis (TB) targets. A prodrug, pyrazinamide (PZA) is the only drug, effective in latent TB, recommended in drug resistance and susceptible Mycobacterium tuberculosis (MTB) isolates. The prodrug conversion into active form, pyrazinoic acid (POA), required the activity of pncA gene encoded pyrazinamidase (PZase).

Artificial Neural Networks for Prediction of Tuberculosis Disease.

The global burden of tuberculosis (TB) and antibiotic resistance is attracting the attention of researchers to develop some novel and rapid diagnostic tools. Although, the conventional methods like culture are considered as the gold standard, they are time consuming in diagnostic procedure, during which there are more chances in the transmission of disease. Further, the Xpert MTB/RIF assay offers a fast diagnostic facility within 2 h, but due to low sensitivity in some sample types may lead to more serious state of the disease.

Exploring the Pyrazinamide Drug Resistance Mechanism of Clinical Mutants T370P and W403G in Ribosomal Protein S1 of Mycobacterium tuberculosis.

Pyrazinamide (PZA) is an essential first line antitubercular drug, which plays a crucial role in tuberculosis treatment. The PZA, which is considered as a pro-drug needs an enzyme of mycobacterial pyrazinamidase (PZase) for its conversion into an active form pyrazinoic acid. Further, this active form of PZA inhibits the ribosomal proteins S1, which facilitates the transfer-mRNA complex formation throughout the translation.

Pyrazinamide resistance and mutations in pncA among isolates of Mycobacterium tuberculosis from Khyber Pakhtunkhwa, Pakistan.

Background: Pyrazinamide (PZA) is an important component of first-line drugs because of its distinctive capability to kill subpopulations of persistent Mycobacterium tuberculosis (MTB). The prodrug (PZA) is converted to its active form, pyrazinoic acid (POA) by MTB pncA-encoded pyrazinamidase (PZase). Mutation in pncA is the most common and primary cause of PZA resistance.

De-Novo Ligand Design against Mutated Huntington Gene by Ligand-based Pharmacophore Modeling Approach.

Background: Huntington's disease is characterized by three side effects, including motor disturbances, psychiatric elements, and intellectual weakness. The onset for HD has nonlinear converse associations with the number of repeat sequences of the polyglutamine mutations, so that younger patients have a tendency for longer repeats length. This HD variation is because of the development of a polyglutamine (CAG) repeats in the exon 1 of the Huntingtin protein.

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).

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.

Prevalence of Pyrazinamide Resistance in Khyber Pakhtunkhwa, Pakistan.

Aims: Pyrazinamide (PZA) is an important component of first-line tuberculosis (TB) treatment because of its distinctive capability to kill subpopulations of persister Mycobacterium tuberculosis (MTB). The significance of PZA can be understood by its inclusion in the most recent World Health Organization-recommended multidrug-resistant (MDR) TB regimen. Very little information is available about the prevalence of PZA-resistant TB from geographically distinct regions of high burden countries, including Khyber Pakhtunkhwa (KPK), Pakistan, because drug susceptibility testing (DST) of PZA is not regularly performed due to the complexity.

Amplification of Mitochondrial DNA for detection of Plasmodiumvivax in Balochistan.

Objective: To access a new step using PCR to amplify the targeted mtDNA sequence for detecting specifically Plasmodium vivax and its co-infections, false positive and false negative results with Plasmodium falciparum.

Methods: In this study we have standardized a new technical approach in which the target mitochondrial DNA sequence (mtDNA) was amplified by using a PCR technique as a tool to detect Plasmodium spp. Species specific primers were designed to hybridize with cytochrome c oxidase gene of P.

Cytogenetic insights into DNA damage and repair of lesions induced by a monomethylated trivalent arsenical.

Arsenic is a human carcinogen, and only recently animal models have been developed that are useful in investigating its carcinogenic mode of action (MOA). However, how arsenic induces cancer is still an open question. In a previous paper, we proposed a model detailing how arsenic might induce DNA lesions leading to cytogenetic damage [A.